Factor Alpha (factor + alpha)

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Factor Alpha

  • growth factor alpha
  • necrosis factor alpha
  • tumor necrosis factor alpha
  • tumour necrosis factor alpha


  • Selected Abstracts


    Development of N-2,4-Pyrimidine-N-phenyl-N,-alkyl Ureas as Orally Active Inhibitors of Tumor Necrosis Factor Alpha (TNF-,) Synthesis.

    CHEMINFORM, Issue 39 2006
    Part 2.
    Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source]


    DNA damage and TNF, cytokine production in hairdressers with contact dermatitis

    CONTACT DERMATITIS, Issue 3 2005
    Delia Cavallo
    The present work was undertaken to study in hairdressers exposed to several irritants and allergens (prevalently hair-dyeing) and affected by hand contact dermatitis the possible correlation between exposure and direct-oxidative DNA damage, production of tumour necrosis factor alpha (TNF,) and allergic inflammatory disease. We evaluated in 19 hairdressers with hand contact dermatitis, 14 allergic contact dermatitis (ACD) and 5 irritant contact dermatitis (ICD) and in a selected control group TNF, serum levels by ELISA and direct-oxidative DNA damage by Fpg (formamido-pyrimidine-glycosylase)-modified Comet test on blood. Hairdressers were divided on the basis of number of hair-dyeing carried out weekly into 2 groups: low-exposure (<60 hair-dyeing/week) and high-exposure hairdressers (,60 hair-dyeing/week) that reflect also the exposure to other allergens and irritants and 2 different tasks (hairdressers and apprentice hairdressers, respectively). Serum levels of TNF, in hairdressers with ACD were significantly higher than controls with a correlation to exposure level. Significant DNA damage in ICD hairdressers with higher exposure as compared to controls was found. These findings suggest that occupational exposure can induce in hairdressers, particularly ICD, DNA damage, increase the TNFa levels particularly in ACD and induce allergic sensitization, suggesting a relationship between direct-oxidative DNA damage, TNF, production and allergic inflammatory disease. [source]


    Monocytes and T lymphocytes contribute to a predominance of interleukin 6 and interleukin 10 in systemic lupus erythematosus,

    CYTOMETRY, Issue 4 2009
    Susana Mellor-Pita
    Abstract Objective To investigate the contribution of T lymphocytes and monocytes to cytokine production in systemic lupus erythematosus (SLE). Methods Forty-five SLE patients and 19 healthy volunteers were included. Serum levels of tumor necrosis factor alpha (TNF,), interferon gamma (IFN,), interleukin (IL)-6, and IL10 were quantified by ELISA. The cytokine production capacities of peripheral blood mononuclear cells were assessed by culturing in vitro with PMA+Ionomycin or LPS. The intracellular cytokine expression was measured by flow cytometry in T lymphocytes and monocytes, respectively. The influence of the disease activity (measured as the SLE-disease activity index; SLEDAI) and the treatment the patients were receiving was evaluated. Results Serum IL10, IL6, and TNF, levels were increased in patients (P , 0.01), and a higher spontaneous (without stimuli) intracellular expression of IL10 in CD4+ and CD8+ T lymphocytes (P < 0.05) and of IL6 in monocytes (P = 0.01) were found. After stimulation, patients presented a higher percentage of CD4+ and CD8+ T lymphocytes producing IL4 and IL10 (P , 0.01), and of monocytes producing IL6 (P = 0.04) and IL10 (P = 0.008). The SLEDAI score was positively correlated with the percentage of CD4+IL10+ and CD8+IL10+ T lymphocytes (P < 0.01), and inversely correlated with CD8+TNF,+ (P= 0.02), CD4+IFN,+ (P = 0.04) and CD8+ IFN,+ (P = 0.002) T lymphocytes. Patients receiving high dose prednisone produced higher IL10, but they also were the patients with a more active disease. Conclusion Monocytes and T lymphocytes (CD4+ and CD8+) contribute to an overproduction of IL6 and IL10 in SLE; this correlates with the disease activity but is independent of the treatment the patients are receiving. © 2009 Clinical Cytometry Society [source]


    Restricted expression of Fgf16 within the developing chick inner ear

    DEVELOPMENTAL DYNAMICS, Issue 8 2006
    Susan C. Chapman
    Abstract Fibroblast growth factor (FGF) signaling is required for otic placode induction and patterning of the developing inner ear. We have cloned the chick ortholog of Fgf16 and analyzed its expression pattern in the early chick embryo. Expression is restricted to the otic placode and developing inner ear through all the stages examined. By the closed otocyst stage, expression has resolved to anterior and posterior domains that partially overlap with those of bone morphogenetic protein 4 (Bmp4), a marker of the developing sensory patches, the cristae of the anterior and posterior semicircular canals. Platelet-derived growth factor alpha (PDGFA), another growth factor with restricted otic expression, also overlaps with Fgf16 expression. The restricted expression pattern of Fgf16 suggests a role for FGF signaling in the patterning of the sensory cristae, together with BMP signaling. Developmental Dynamics 235:2276,2281, 2006. © 2006 Wiley-Liss, Inc. [source]


    An increased proportion of inflammatory cells express tumor necrosis factor alpha in idiopathic achalasia of the esophagus

    DISEASES OF THE ESOPHAGUS, Issue 5 2009
    A. Kilic
    SUMMARY Achalasia is a motility disorder characterized by the absence of coordinated peristalsis and incomplete relaxation of the lower esophageal sphincter. The etiology remains unclear although dense inflammatory infiltrates within the myenteric plexus have been described. The nature of these infiltrating cells is unknown. The aim of this study was to evaluate the expression of proinflammatory cytokines , namely, tumor necrosis factor alpha and interleukin-2 , in the distal esophageal muscle in patients with achalasia. Lower esophageal sphincter muscle from eight patients undergoing myotomy or esophagectomy for achalasia of the esophagus were obtained at the time of surgery. Control specimens consisted of similar muscle taken from eight patients undergoing operation for cancer or Barrett's esophagus. The expression of tumor necrosis factor alpha and interleukin-2 were assessed by immunohistochemistry. The total number of inflammatory cells within the myenteric plexus were counted in five high power fields. The percentage of infiltrating cells expressing tumor necrosis factor alpha or interleukin-2 was calculated. Clinical data including demographics, preoperative lower esophageal sphincter pressure, duration of symptoms, and dysphagia score (1 = no dysphagia to 5 = dysphagia to saliva) were obtained through electronic medical records. Statistical comparisons between the groups were made using the unpaired t -test, Fisher's exact test, or Mann,Whitney U test, with a two-tailed P -value less than 0.05 being considered significant. The total number of inflammatory cells was found to be similar between the groups. A significantly higher proportion of inflammatory cells expressed tumor necrosis factor alpha in achalasia as compared with controls (22 vs. 11%; P= 0.02). A similar percentage of infiltrating cells expressed interleukin-2 (40 vs. 41%; P= 0.87). Age, gender, preoperative lower esophageal sphincter pressure, or dysphagia score were not correlated to expression of these cytokines. There was, however, a significant inverse correlation between duration of symptoms and the proportion of inflammatory cells expressing tumor necrosis factor alpha in achalasia (P= 0.007). In conclusion, a higher proportion of infiltrating inflammatory cells expressed tumor necrosis factor alpha in achalasia. Furthermore, this proportion appears to be highest early in the disease process. Further studies are required to more clearly delineate the role of tumor necrosis factor alpha in the pathogenesis of this idiopathic disease. [source]


    NF,B, cytokines, TLR 3 and 7 expression in human end-stage HCV and alcoholic liver disease

    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2010
    Peter Stärkel
    Eur J Clin Invest 2010; 40 (7): 575,584 Abstract Background/aims, Conflicting observations exist concerning the role of nuclear factor kappa B (NF,B) in alcoholic liver disease (ALD) in animal models. To date no studies have examined this aspect in human liver tissue. We here assessed cytokines and toll-like receptors (TLRs) expressions in conjunction with NF,B activation in non-active end-stage human ALD compared with normal livers and hepatitis C virus (HCV) related end-stage disease. Methods, mRNA and protein expression were examined by quantitative PCR and Western blotting, DNA-binding by electrophoretic mobility shift assays and NF,B sub-cellular localization by immunofluorescent staining of livers. Results, NF,B mRNA and protein expression as well as strong DNA-binding were preserved in ALD but significantly down-regulated in HCV compared with normal livers. P50 immunofluorescence was found in hepatocytes and bile ducts in ALD and normal livers, whereas a shift was observed in p65 staining from non-parenchymal cells in normal livers to hepatocytes in ALD. NF,B responsive genes mRNA levels IkB, and interleukin 6 were significantly higher in ALD compared with HCV. Tumour necrosis factor alpha (TNF,), TLRs 3 and 7 mRNA were up-regulated in ALD and HCV compared with normal liver with TNF, and TLR7 being the highest in HCV. Strong induction of interferon beta was found in HCV but not in ALD or normal liver tissue. Conclusions, Persistent NF,B activation together with high pro-inflammatory cytokine expression and upregulation of TLR3 and TLR7 is associated with end-stage ALD in humans and could contribute to disease progression even in absence of alcohol intake. [source]


    22-ene-25-oxa-vitamin D: a new vitamin D analogue with profound immunosuppressive capacities

    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2005
    C. Daniel
    Abstract Background, The biologic role of 1,25-dihydroxyvitamin D3, such as anti-inflammatory functions, reduction of cytokine production by T cells and immunoglobulin production by B cells, is well established. However, its clinical use as an immunosuppressive agent is limited because of the hypercalcemic toxicity occurring after systemic application. The purpose of this study was to investigate the immunmodulatory effects of 22-ene-25-oxa-vitamin D (ZK156979), a novel low calcemic vitamin D analogue. Materials and methods, Human peripheral blood mononuclear cells (PBMCs) from healthy donors were isolated using the Ficoll Hypaque technique, cultured for 24 h and treated with different concentrations of ZK156979 ranging from 10,5 to 10,10 mol L,1 compared with 1,25-dihydroxyvitamin D3[10,5,10,10 mol L,1] following phytohaemagglutinin (PHA) stimulation. Interferon gamma (IFN,), tumour necrosis factor alpha (TNF,), interleukin 1 beta (IL-1,), interleukin 10 (IL-10) and interleukin 4 (IL-4) secretion in supernatants were measured by ELISA. Results, ZK156979 inhibited the PHA-induced Th1-response (IFN, and TNF, levels) and the macrophage-product IL-1, in a concentration-dependent manner (10,10,10,5 mol L,1) with the efficiency on cytokine expression compared with 1,25-dihydroxyvitamin D3 being slightly reduced. In contrast, ZK156979 and 1,25-dihydroxyvitamin D3 both affected the Th2 response, leading to significantly increased IL-10- and IL-4 secretion. Conclusions, ZK156979 is a member of novel vitamin D analogues revealing prominent immunomodulatory and suppressive characteristics with distinctive inhibition of Th1-cytokines whereas the Th2 compartment is augmented, thus providing a considerable therapeutic potential in T-cell -mediated diseases. [source]


    Microglial glutamate uptake is coupled to glutathione synthesis and glutamate release

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2006
    Mikael Persson
    Abstract The physiological function of microglial glutamate uptake has been debated as it is about 10% of that measured for astrocytes. This study addresses how glutamate, taken up from the extracellular space, is utilized by microglia. It was found that purified rat microglia incubated for 60 min with 3H-glutamate had an increased intracellular accumulation of 3H-glutamate after 12 h incubation with tumour necrosis factor alpha (TNF-,) but not after incubation with lipopolysaccharide (LPS). Furthermore, LPS- but not TNF-,-treated cells showed an increased efflux of 3H-labelled compounds, presumably glutamate through the XC, system and treatment with LPS or TNF-, increased the microglial glutathione concentrations and led to an increased incorporation of 3H-glutamate into glutathione. Depending on the stimuli, 3,6% of the total labelled contents were found in the form of glutathione and 25,35% in the form of glutamate. These results show that microglial glutamate uptake is directly coupled to glutathione synthesis and release of glutamate and/or glutamate metabolites. Additionally, the increased glutathione contents after LPS or TNF-, treatment were able to reduce microglial cell death after H2O2 challenge, showing a potential (self)-protective function for microglial glutamate transporter expression and glutathione synthesis. [source]


    Erythropoietin reduces Schwann cell TNF-,, Wallerian degeneration and pain-related behaviors after peripheral nerve injury

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2006
    W. Marie Campana
    Abstract Chronic sciatic nerve constriction injury (CCI) induces Wallerian degeneration and exaggerated pain-like behaviors. These effects are mediated in large part by pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-,). In this study, we demonstrate that systemically administered recombinant human erythropoietin (rhEpo) facilitates recovery from chronic neuropathic pain associated with CCI in rats. Because TNF-, has been implicated in the development of pain-related behaviors, we measured TNF-, mRNA at the nerve injury site. Systemically or locally administered rhEpo decreased TNF-, mRNA, compared with that observed in untreated animals. RhEpo also significantly (P < 0.05) decreased axonal degeneration. Immunohistochemistry of CCI nerve showed abundant TNF-, in Schwann cells, axoplasm and macrophages. In rhEpo-treated animals, TNF-, immunopositivity was decreased selectively in Schwann cells. These results suggest a model in which rhEpo counteracts the effects of TNF-, in CCI by blocking expression of TNF-, in Schwann cells. To further test this model, we studied primary Schwann cell cultures. RhEpo inhibited TNF-, expression in response to lipopolysaccharide, supporting the conclusions of our in vivo CCI experiments. In addition, rhEpo directly counteracted Schwann cell death induced by exogenously added TNF-,in vitro. These results indicated that rhEpo regulates TNF-, by multiple mechanisms; rhEpo regulates TNF-, mRNA expression by Schwann cells but also may directly counteract TNF-, signaling pathways that lead to injury, chronic pain and/or death. [source]


    Hypoxia-activated microglial mediators of neuronal survival are differentially regulated by tetracyclines

    GLIA, Issue 8 2006
    Aaron Y. Lai
    Abstract The tetracycline derivatives minocycline (MINO) and doxycycline (DOXY) have been shown to be neuroprotective in in vivo and in vitro models of stroke. This neuroprotection is thought to be due to the suppression of microglial activation. However, the specific molecular parameters in microglia of the tetracyclines' effect are not understood. We subjected cultured rat microglial and neuronal cells to in vitro hypoxia and examined the effects of MINO and DOXY pre-treatments. Our data showed that MINO and DOXY protect against hypoxia-induced neuronal death by a mechanism dependent on regulation of microglial factors, but likely unrelated to regulation of microglial proliferation/viability. Both MINO and DOXY suppressed the hypoxic activation of ED-1, a marker for microglial activation. Morphological analyses of hypoxic microglia using the microglial marker Iba1 revealed that treatment with MINO and DOXY caused a higher percentage of microglia to remain in a non-activated state. MINO suppressed the hypoxic upregulation of pro-inflammatory agents nitric oxide (NO), interleukin-1 beta (IL-1,), and tumor necrosis factor alpha (TNF-,), while DOXY down-regulated only NO and IL-1,. In contrast, the hypoxic activation of pro-survival/neuroprotective microglial proteins, such as brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), were unaffected by tetracycline treatments. Taken together, these results suggest that MINO and DOXY may provide neuroprotection against stroke by selectively down-regulating microglial toxic factors while maintaining functional pro-survival factors. © 2006 Wiley-Liss, Inc. [source]


    Favorable effect of adefovir on the number and functionality of myeloid dendritic cells of patients with chronic HBV,

    HEPATOLOGY, Issue 4 2006
    Renate G. van der Molen
    In patients with chronic hepatitis B virus (HBV), 2 predominant precursor dendritic cell (DC) subtypes, the myeloid dendritic cell (mDC) and the plasmacytoid dendritic cell (pDC), were recently found to be functionally impaired. HBV DNA was found to be present in the DC subtypes, but no viral replication could be detected. The question remains whether simply the presence of the virus and viral proteins causes this dysfunction of DCs. To address this issue, the effect of viral load reduction resulting from treatment with the nucleotide analogue adefovir dipivoxil on the number and functionality of circulating DCs was studied during 6 months of treatment. Treatment resulted in a mean 5 log10 decrease in the viral load and normalization of alanine aminotransferase within 3 months. The number of mDCs, but not of pDCs, increased significantly over 6 months of treatment to a level comparable to that of uninfected healthy controls. The allostimulatory capacity of isolated and in vitro matured mDCs increased significantly after 3 months of treatment. Accordingly, mDCs exhibited an increased capacity to produce tumor necrosis factor alpha and interleukin-12 after 3-6 months of treatment. There was no change in interferon alpha production by pDCs during treatment. In conclusion, adefovir treatment results in an improvement in the number and functionality of mDCs, but not of pDCs. Our findings provide clues for the reasons why current antiviral therapy does not lead to consistently sustained viral eradication. (HEPATOLOGY 2006;44:907,914.) [source]


    Hepatocytes as cytotoxic effector cells can induce cell death by CD95 ligand-mediated pathway,

    HEPATOLOGY, Issue 6 2006
    Clifford S. Guy
    The liver plays an increasingly recognized role in the host's immune responses. The direct contribution of hepatocytes as effector cells to local immunity, pathogen containment, and liver disease is not determined. This in vitro study examined whether hepatocytes can eliminate other cells via a CD95 ligand (CD95L or FasL)/CD95 (Fas),mediated mechanism and whether this cytotoxic activity can be modulated by cytokines such as interferon gamma (IFN-,) or tumor necrosis factor alpha (TNF-,). We have found that normal woodchuck and human hepatocytes, both cultured and primary freshly isolated, as well as human HepG2 cells, intrinsically transcribe not only CD95 but also CD95L when examined by reverse transcription-polymerase chain reaction (RT-PCR) assays. The functional competence of CD95L, which was detectable in hepatocytes and HepG2 cells by Western blotting, was confirmed in bioassays by induction of apoptosis of CD95-bearing P815 and LS102.9 cell targets and validated by inhibition of the cell killing with CD95 antagonistic antibody or with a general caspase inhibitor. Furthermore, exposure of cultured hepatocytes to IFN-, or their stable transfection with IFN-, cDNA or TNF-, cDNA increased hepatocyte CD95L/CD95,mediated cell killing. In conclusion, hepatocytes express both CD95L and CD95 and they can induce death of other cells by a CD95L-dependent mechanism. IFN-, and, to a lesser extent, TNF-, can enhance hepatocyte CD95L-mediated cytotoxicity. This suggests that the local cytokine environment may modulate the hepatocyte contribution to liver immunity. (HEPATOLOGY 2006;43:1231,1240.) [source]


    Leflunomide protects from T-cell,mediated liver injury in mice through inhibition of nuclear factor ,B

    HEPATOLOGY, Issue 5 2004
    Motoaki Imose
    Leflunomide is a novel immunosuppressive and anti-inflammatory agent for the treatment of autoimmune disease. The aim of this study was to investigate whether leflunomide protects from liver injury induced by concanavalin A (Con A), a T-cell,dependent model of liver damage. BALB/c mice were injected with 25 mg/kg Con A in the presence or absence of 30 mg/kg leflunomide. Liver injury was assessed biochemically and histologically. Levels of circulating cytokines and expressions of cytokine messenger RNA (mRNA) in the liver and the spleen were determined. Treatment with leflunomide markedly reduced serum transaminase activities and the numbers of dead liver cells. Leflunomide significantly inhibited increases in plasma tumor necrosis factor alpha (TNF-,) and interleukin 2 concentrations, and also reduced TNF-, mRNA expression in the liver after administration of Con A. These findings were supported by the results in which leflunomide administration decreased the number of T lymphocytes infiltrating the liver as well as inhibiting their production of TNF-,. Activation of nuclear factor ,B (NF-,B), which regulates TNF-, production, was inhibited in the liver of mice treated with leflunomide, resulting in a reduction of TNF-, production from lymphocytes infiltrating the liver. In conclusion, leflunomide is capable of regulating T-cell,mediated liver injury in vivo and that this event may depend on the decrease of TNF-, production in the liver through inhibition of NF-,B activation caused by leflunomide. (HEPATOLOGY 2004.) [source]


    A psychoneuroimmunological review on cytokines involved in antidepressant treatment response

    HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 3 2010
    Debbie G. A. Janssen
    Abstract Objectives The literature exploring the role that cytokine functioning plays in the pathogenesis and treatment of depressive illness is reviewed. The review focuses on the influence of antidepressants on cytokines, and on how treatment response might be affected by genetic variants of cytokines. Method The authors systematically reviewed the scientific literature on the subject over the last 20 years, searching PubMed, PsychInfo, and Cochrane databases. Results Antidepressants modulate cytokine functioning, and these mechanisms appear to directly influence treatment outcome in depression. Antidepressants appear to normalize serum levels of major inflammatory cytokines, including interleukin (IL)-1,, IL-6, tumor necrosis factor alpha (TNF- ,), and interferon gamma (IFN- ,). Antidepressants are postulated to modulate cytokine functioning through their effects on intracellular cyclic adenosyl monophosphate (cAMP), serotonin metabolism, the hypothalamo-pituitary-adrenocortical (HPA) axis or through a direct action on neurogenesis. Preliminary research shows that cytokine genotypes and functioning may be able to help predict antidepressant treatment response. Conclusions Current literature demonstrates an association between antidepressant action and cytokine functioning in major depression. Improved understanding of the specific pharmacologic and pharmacogenetic mechanisms is needed. Such knowledge may serve to enhance our understanding of depression, leading to promising new directions in the pathology, nosology, and treatment of depression. Copyright © 2010 John Wiley & Sons, Ltd. [source]


    Preserved Na+/H+ exchanger isoform 3 expression and localization, but decreased NHE3 function indicate regulatory sodium transport defect in ulcerative colitis,

    INFLAMMATORY BOWEL DISEASES, Issue 7 2010
    Sunil Yeruva PhD
    Abstract Background: A major causative factor of diarrhea in ulcerative colitis (UC) patients is the loss of Na+ absorptive capacity of the inflamed colonic mucosa. Potential contributing mechanisms include reduced driving force for active transport, and impaired expression, mislocalization, or defective transport function of Na+ absorptive proteins. We therefore studied the expression, brush border membrane (BBM) localization, and transport capacity of the major intestinal Na+ absorptive protein, the Na+/H+ exchanger isoform 3 (NHE3) in biopsies from UC patients. Methods: In UC and control biopsies, inflammation was graded histologically, NHE3, tumor necrosis factor alpha (TNF-,), villin, as well as other housekeeping genes were analyzed by quantitative real-time polymerase chain reaction (PCR), BBM localization of NHE3 determined by immunohistochemistry, and confocal microscopy. Na+ absorptive capacity was assessed by 22Na+ isotope fluxes and NHE3 transport activity measured microfluorometrically in BCECF-loaded surface colonocytes within isolated crypts. Results: In mildly, moderately, and severely inflamed sigmoid colon of UC patients, neither NHE3 mRNA expression nor the abundance of NHE3 in the BBM was significantly altered compared to other structural components of the BBM. However, Na+ absorption was strongly reduced by ,80% and acid-activated NHE3 transport activity was significantly decreased in the surface cells of sigmoid colonic crypts even in moderately inflamed mucosa. Conclusions: In the colonic mucosa of patients with active UC, NHE3 transport capacity was found significantly decreased despite correct NHE3 location and abundance in the brush border, independent of current treatment. These findings suggest functional NHE3 transport as a novel factor for inflammatory diarrhea in UC patients. (Inflamm Bowel Dis 2010) [source]


    In vivo analysis of gut function and disease changes in a zebrafish larvae model of inflammatory bowel disease: A feasibility study

    INFLAMMATORY BOWEL DISEASES, Issue 7 2010
    Angeleen Fleming PhD
    Abstract Background: The aim of this study was to develop a model of inflammatory bowel disease (IBD) in zebrafish larvae, together with a method for the rapid assessment of gut morphology and function in vivo thereby enabling medium-throughput compound screening. Methods: Assays were performed using larval zebrafish from 3,8 days postfertilization (d.p.f.) in 96-well plates. Gut morphology and peristalsis were observed in vivo using fluorescent imaging following ingestion of fluorescent dyes. IBD was induced by addition of 2,4,6-trinitrobenzenesulfonic acid (TNBS) to the medium within the well. Pathology was assessed in vivo using fluorescent imaging and postmortem by histology, immunohistochemistry, and electron microscopy. Therapeutic compounds were evaluated by coadministration with TNBS. Results: A novel method of investigating gut architecture and peristalsis was devised using fluorescent imaging of live zebrafish larvae. Archetypal changes in gut architecture consistent with colitis were observed throughout the gut. Significant changes in goblet cell number and tumor necrosis factor alpha (TNF-,) antibody staining were used to quantify disease severity and rescue. Prednisolone and 5-amino salicylic acid treatment ameliorated the disease changes. Candidate therapeutic compounds (NOS inhibitors, thalidomide, and parthenolide) were assessed and a dissociation was observed between efficacy assessed using a single biochemical measure (TNF-, staining) versus an assessment of the entire disease state. Conclusions: Gut physiology and pathology relevant to human disease state can be rapidly modeled in zebrafish larvae. The model is suitable for medium-throughput chemical screens and is amenable to genetic manipulation, hence offers a powerful novel premammalian adjunct to the study of gastrointestinal disease. (Inflamm Bowel Dis 2010) [source]


    Localization of substance P-induced upregulated interleukin-8 expression in human dental pulp explants

    INTERNATIONAL ENDODONTIC JOURNAL, Issue 2 2008
    G. T.-J.
    Abstract Aim, To localize ex vivo expression of interleukin-8 (IL-8) induced by substance P (SP) in human dental pulps. Methodology, Intact caries-free, freshly extracted third molars (n = 20) were collected from patients (15,25 years old). The teeth were split and pulpal tissue was obtained and stored in Dulbecco's modified Eagle medium. Human dental pulp tissue explants were stimulated with SP. Expression of IL-8 in pulp explants was detected and localized by immunohistochemistry. Results, Moderated IL-8 immunoreactivities were detected mainly in the cell-rich zone in pulp tissues 12 h after tumour necrosis factor alpha (TNF-,) stimulation (positive controls), whereas only weak IL-8 expression was observed in tissues stimulated with SP at the same time interval. These data did not differ from those in negative controls. Increased IL-8 expression in pulp explants after 24 h of SP stimulation was noted compared with negative controls and located in fibroblast-like cells, blood vessel-associated cells and extracellular matrix in the central zone and cell-rich zone of pulp explants. Tissues stimulated with TNF-, for 24 h (positive controls) revealed weak IL-8 immunoreactivities with altered cell morphology. Conclusions, Substance P induces IL-8 expression and was located in fibroblast-like pulp cells, blood vessel-associated cells and extracellular matrix of human dental explants. These data support the hypothesis that neuropeptide (SP) coordinates the modulation of pulpal inflammation via up-regulating chemokine IL-8. [source]


    Effects of tumour necrosis factor alpha and interleukin-6 on progesterone and calcium ionophore-induced acrosome reaction

    INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 3 2009
    F. Lampiao
    Summary For human spermatozoa to successfully fertilize the oocyte, they need to undergo a timely acrosome reaction (AR). Factors which disturb the AR may lead to fertilization failure. The objective of this study was to investigate the effects of two cytokines namely tumour necrosis factor alpha (TNF-,) and interleukin-6 (IL-6) on the spontaneous, calcium ionophore-induced and progesterone-induced human sperm AR. Twenty-two normal semen samples were treated with increasing concentrations of TNF-, and IL-6 after spermatozoa were isolated by a double wash swim-up method. The AR was induced by calcium ionophore A23187 and progesterone. The AR was determined by using fluorescein isothiacyanate Pisum sativum agglutinin and observed under fluorescence microscope. Both TNF-, and IL-6 could decrease the spontaneous, ionophore and progesterone-induced AR (p < 0.05) in a dose-dependent manner. TNF-, showed a more potent inhibiting effect than IL-6 by inhibiting the AR at lower concentrations. This study has demonstrated that TNF-, and IL-6 play a role in inhibiting both the non-physiological as well as physiologically elicited AR by calcium ionophore and progesterone respectively. [source]


    Muscle Endurance in Elderly Nursing Home Residents Is Related to Fatigue Perception, Mobility, and Circulating Tumor Necrosis Factor-Alpha, Interleukin-6, and Heat Shock Protein 70

    JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 3 2008
    (See editorial comments by Drs. Hermes Florez, Bruce R. Troen, pp 55
    OBJECTIVES: To explore the relationships between muscle endurance and circulating interleukin (IL)-6, tumor necrosis factor alpha (TNF-,), and heat shock protein (Hsp)70 in nursing home residents and to assess how muscle endurance relates to self-perceived fatigue and mobility. DESIGN: Exploratory study. SETTING: Three nursing homes of the Foundation for Psychogeriatrics (Brussels, Belgium). PARTICIPANTS: Seventy-seven residents (53 female and 24 male, mean age 81 ± 8). MEASUREMENTS: Participants were assessed for muscle endurance (fatigue resistance and grip work); perceived fatigue (visual analogue scale for fatigue); fatigue during daily activities (Mobility-Tiredness Scale); effect of fatigue on quality of life (World Health Organization Quality Of Life questionnaire); mobility (Tinetti Test & Elderly Mobility Scale (EMS)); and circulating IL-6, TNF-,, and Hsp70. RESULTS: Residents with better fatigue resistance reported less self-perceived tiredness (P<.05). Similar trends were observed for fatigue during daily activities and for the extent to which fatigue bothered subjects. Higher grip work was associated with less self-perceived fatigue on all fatigue scales (P<.01). Fatigue resistance and grip work were positively related to balance and basic mobility (all P<.01; trend for relationship between fatigue resistance and EMS). Subjects with high IL-6 and Hsp70 showed significantly worse fatigue resistance (P=.007) and muscle work (P=.045) than those with high IL-6 and low Hsp70. In male residents, higher TNF-, was related to worse fatigue resistance and grip work (P<.05). CONCLUSION: Elderly nursing home residents complaining of fatigue need to be taken seriously, because they show worse muscle endurance, which is related to poorer mobility. Inflammatory processes involving TNF-, and the interaction between IL-6 and Hsp70 are related to poorer muscle endurance in these patients. [source]


    Comparison of the effects of erdosteine and N-acetylcysteine on apoptosis regulation in endotoxin-induced acute lung injury

    JOURNAL OF APPLIED TOXICOLOGY, Issue 4 2006
    Rezan Demiralay
    Abstract This study was carried out to investigate comparatively the frequency of apoptosis in lung epithelial cells after intratracheal instillation of endotoxin [lipopolysaccharide (LPS)] in rats and the role of tumor necrosis factor alpha (TNF- ,) on apoptosis, and the effects of erdosteine and N-acetylcysteine on the regulation of apoptosis. Female Wistar rats were given oral erdosteine (10,500 mg kg,1) or N-acetylcysteine (10,500 mg kg,1) once a day for 3 consecutive days. Then the rats were intratracheally instilled with LPS (5 mg kg,1) to induce acute lung injury. The rats were killed at 24 h after LPS administration. Lung tissue samples were stained with hematoxylin-eosin for histopathological assessments. The apoptosis level in the lung bronchial and bronchiolar epithelium was determined using the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabelling) method. Cytoplasmic TNF- , was evaluated by immunohistochemistry. Pretreatment with erdosteine and pretreatment with N-acetylcysteine at a dose of 10 mg kg,1 had no protective effect on LPS-induced lung injury. When the doses of drugs increased, the severity of the lung damage caused by LPS decreased. It was found that as the pretreatment dose of erdosteine was increased, the rate of apoptosis induced by LPS in lung epithelial cells decreased and this decrease was statistically significant in doses of 300 mg kg,1 and 500 mg kg,1. Pretreatment with N-acetylcysteine up to a dose of 500 mg kg,1 did not show any significant effect on apoptosis regulation. It was noticed that both antioxidants had no significant effect on the local production level of TNF- ,. These findings suggest that erdosteine could be a possible therapeutic agent for acute lethal lung injury and its mortality. Copyright © 2006 John Wiley & Sons, Ltd. [source]


    Modulation of sulfur mustard induced cell death in human epidermal keratinocytes using IL-10 and TNF-,,,

    JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2005
    Aziz Qabar
    Abstract We compared the effects of overexpressing a tightly regulated anti-inflammatory cytokine, interleukin 10 (IL-10), and the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-,) on sulfur mustard induced cytotoxicity in human epidermal keratinocytes. Both cytokines were overexpressed when compared with the cells transfected with the empty vector as determined by quantitative ELISA. Cells overexpressing interleukin 10 suppressed the pro-inflammatory cytokines interleukin 8 and interleukin 6 following exposure to 50,300 ,M sulfur mustard. These cells exhibited delayed onset of sulfur mustard induced cell death. On the other hand, cells overexpressing tumor necrosis factor alpha induced a sustained elevation in both interleukin 6 and 8 expression following exposure to 50,300 ,M sulfur mustard. These cells were sensitized to the effects of sulfur mustard that resulted in an increased sulfur mustard induced cell death. Normal human epidermal keartinocytes treated with sulfur mustard exhibited elevated levels of tumor necrosis factor alpha expression and increased activity of nuclear factor kappa B. Gene array data indicated that cells overexpressing interleukin 10 induced several genes that are involved in growth promotion and cell-fate determination. We, therefore, identify IL-10 and TNF-, signal transduction pathways and their components as possible candidates for early therapeutic intervention against sulfur mustard induced cell injury. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:213,225, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20089 [source]


    Updating the effects of fatty acids on skeletal muscle

    JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2008
    Leonardo R. Silveira
    In this review we updated the fatty acid (FA) effects on skeletal muscle metabolism. Abnormal FA availability induces insulin resistance and accounts for several of its symptoms and complications. Efforts to understand the pathogenesis of insulin resistance are focused on disordered lipid metabolism and consequently its effect on insulin signaling pathway. We reviewed herein the FA effects on metabolism, signaling, regulation of gene expression and oxidative stress in insulin resistance. The elevated IMTG content has been associated with increased intracellular content of diacylglycerol (DAG), ceramides and long-chain acyl-coenzyme A (LCA-CoA). This condition has been shown to promote insulin resistance by interfering with phosphorylation of proteins of the insulin pathway including insulin receptor substrate-1/2 (IRS), phosphatidylinositol-3-kinase, (PI3-kinase) and protein kinase C. Although the molecular mechanism is not completely understood, elevated reactive oxygen (ROS) and nitrogen species (RNS) are involved in this process. Elevated ROS/RNS activates nuclear factor-kappaB (NFkB), which promotes the transcription of proinflammatory tumoral necrosis factor alpha (TNF,), decreasing the insulin response. Therefore, oxidative stress induced by elevated FA availability may constitute one of the major causes of insulin resistance in skeletal muscle. J. Cell. Physiol. 217: 1,12, 2008. © 2008 Wiley-Liss, Inc. [source]


    Activity of the matrix metalloproteinase-9 promoter in human normal and tumor cells

    JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2004
    Cristina Morelli
    Matrix metalloproteinases (MMPs) belong to a family of proteins essential for those processes involving extracellular matrix degradation, such as embryonic development, morphogenesis, and tissue resorption and remodeling. Some members of this family play a crucial role also in tumor invasion. Most notably, MMP-9 is expressed in invasive tumors, and represents a key protein in brain tumor progression, whereas it is not expressed in adult normal tissues. The expression of the MMP-9, like other members of the family, is transcriptionally regulated. We, therefore, postulated that the MMP-9 promoter could be useful in driving selective expression of exogenous genes in tumor cells. This represents a key feature for gene therapy applications, since currently employed viral promoters induce severe organ toxicity, limiting the clinical benefits. In this study, we investigated the activity of the MMP-9 promoter in driving exogenous gene expression in human cell lines. High levels of reporter gene expression were detected in tumor derived cell lines, whereas the MMP-9 promoter activity in non-tumor cells was negligible. Furthermore, we show that tumor necrosis factor alpha (TNF,) is able to enhance considerably the MMP-9 promoter activity only in tumor cells. Since recent studies have indicated that MMP-9 enzymatic activity is detectable in the blood, it would be possible to screen potential responsive patients for a tumor gene therapy approach based on the MMP-9 promoter. Taken together these data suggest that MMP-9 promoter has the characteristics for transcritpionally targeted and inducible gene therapy applications. J. Cell. Physiol. 199: 126,133, 2004© 2003 Wiley-Liss, Inc. [source]


    Glioma cells under hypoxic conditions block the brain microvascular endothelial cell death induced by serum starvation

    JOURNAL OF NEUROCHEMISTRY, Issue 1 2005
    Yoshifumi Ueda
    Abstract Angiogenesis is one of essential components for the growth of neoplasms, including malignant gliomas. However, tumor vascularization is often poorly organized and marginally functional due to tumor strucutural abnormalities, inducing regional or temporal hypoxic conditions and nutritional shortages in tumor tissues. We investigated how during angiogenesis migrating endothelial cells survive in these hypoxic and reduced nutritional conditions. Human brain microvascular endothelial cells (HBMECs) underwent apoptosis and necrosis after serum withdrawal. This endothelial cell death was blocked by recombinant VEGF protein or the culture medium of U251 glioma cells exposed to hypoxia (H-CM). Hypoxic treatment increased vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNF-,) expression in U251 glioma cells. H-CM activated nuclear factor-,B (NF,B) protein and increased the gene expression of antiapoptotic factors including Bcl-2, Bcl-XL, survivin and X-chromosome-linked inhibitor of apoptosis protein (XIAP) in endothelial cells. The survival activity of H-CM for endothelial cells was abolished by two kinds of VEGF inhibitors {Cyclopeptidic VEGF inhibitor and a VEGF receptor tyrosine kinase inhibitor (4-[(4,-chloro-2,-fluoro) phenylamino]-6, 7-dimethoxyquinazoline)} or NF,B inhibitors (ALLN and BAY 11,7082). These VEGF inhibitors did not block the activation of NF,B induced by H-CM in endothelial cells. On the contrary, TNF-, antagonist WP9QY enhanced the survival activity of H-CM for endothelial cells and blocked NF,B activation induced by H-CM under serum-starved conditions. Taken together, our data suggest that both the secretion of VEGF from glioma cells and activation of NF,B in endothelial cells induced by TNF-, are necessary for endothelial cell survival as they increase the expression of antiapoptotic genes in endothelial cells under conditions of serum starvation. These pathways may be one of the mechanisms by which angiogenesis is maintained in glioma tissues. [source]


    Influences of dopaminergic lesion on epidermal growth factor-ErbB signals in Parkinson's disease and its model: neurotrophic implication in nigrostriatal neurons

    JOURNAL OF NEUROCHEMISTRY, Issue 4 2005
    Yuriko Iwakura
    Abstract Epidermal growth factor (EGF) is a member of a structurally related family containing heparin-binding EGF-like growth factor (HB-EGF) and transforming growth factor alpha (TGF,) that exerts neurotrophic activity on midbrain dopaminergic neurons. To examine neurotrophic abnormality in Parkinson's disease (PD), we measured the protein content of EGF, TGF,, and HB-EGF in post-mortem brains of patients with Parkinson's disease and age-matched control subjects. Protein levels of EGF and tyrosine hydroxylase were decreased in the prefrontal cortex and the striatum of patients. In contrast, HB-EGF and TGF, levels were not significantly altered in either region. The expression of EGF receptors (ErbB1 and ErbB2, but not ErbB3 or ErbB4) was down-regulated significantly in the same forebrain regions. The same phenomenon was mimicked in rats by dopaminergic lesions induced by nigral 6-hydroxydopamine infusion. EGF and ErbB1 levels in the striatum of the PD model were markedly reduced on the lesioned side, compared with the control hemisphere. Subchronic supplement of EGF in the striatum of the PD model locally prevented the dopaminergic neurodegeration as measured by tyrosine hydroxylase immunoreactivity. These findings suggest that the neurotrophic activity of EGF is maintained by afferent signals of midbrain dopaminergic neurons and is impaired in patients with Parkinson's disease. [source]


    Vascular endothelial growth factor (VEGF)-induced angiogenesis in herniated disc resorption

    JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2002
    Hirotaka Haro
    Abstract Intervertebral disc herniation is a major cause of low back pain and sciatica. Spontaneous resorption of herniated disc (HD) is frequently detected by magnetic resonance imaging (MRI). Marked infiltration by macrophages and neo-vascularization are observed upon histogical examination of HD. In addition, enhanced MRI studies suggest that HD resorption occurs more frequently in those completely exposed to the epidural space and that this correlates with their degree of vascularization. We have postulated that the angiogenic factor, vascular endothelial growth factor (VEGF), may be implicated in the neo-vascularization of HD tissues. Here we demonstrate that VEGF and its receptors VEGFR-1 and VEGFR-2 are expressed in human surgical samples of HD. Using a co-culture system comprised of murine peritoneal macrophages and intervertebral disc tissue as a model of the acute phase of HD developed previously, an increase in macrophage VEGF protein and mRNA expression was observed upon exposure to disc tissue. Tumor necrosis factor alpha (TNF-,) was required for this induction of VEGF. Use of a novel angiogenesis assay revealed that addition of the conditioned media from the co-culture system resulted in an increase of vascular tubule formation. This effect was strongly inhibited by anti-VEGF antibody, but augmented by recombinant VEGF. We conclude that VEGF induction, under the co-culture conditions tested can result in neo-vascularization of intervertebral disc tissue and may thus play a role in the resorption of HD. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source]


    A novel bisphosphonate inhibits inflammatory bone resorption in a rat osteolysis model with continuous infusion of polyethylene particles

    JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2002
    Miho Iwase
    Abstract This study examined the inhibitory effect of a new bisphosphonate (TRK-530) on wear debris-mediated bone resorption in a rat osteolysis model involving continuous infusion of high density polyethylene (HDPE) particles. TRK-530 (TRK) is a novel synthetic bisphosphonate that has been shown to decrease the level of tumor necrosis factor alpha (TNF-,) in the bone marrow of rats with adjuvant arthritis. Forty Wistar rats were randomized to two groups (n = 20 each). In each rat, a Kirshner (K) wire was inserted into the femur and HDPE particles were continuously infused into the knee joint. Thereafter, the animals were subcutaneously injected with saline (control group) or 1 mg/kg of TRK (TRK group) every second day, and were sacrificed at 4 or 8 weeks after surgery. Radiographs obtained at the time of sacrifice were evaluated for periprosthetic osteolysis. We also examined the thickness of the reactive membrane as well as the number of osteoclast-like cells around the K-wire. In addition, we examined the expression of genes for bone-resorbing cytokines in the reactive membrane. Radiographic peri-implant osteolysis was more frequent in the control group compared with the TRK group at each time of assessment (p < 0.01). The interfacial membrane was significantly thinner in the TRK group compared with the control group (p < 0.01) and the average number of osteoclast-like cells around the K-wire was significantly fewer in the TRK group (p < 0.01). In addition, the expression of interleukin 1-alpha messenger ribonucleic acid (IL-1, mRNA) and TNF-, mRNA was suppressed in the TRK group at each time of assessment. We conclude that the TRK can inhibit the formation of inflammatory peri-implant osteolysis induced by HDPE particles. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source]


    Influence of subcutaneous administration of recombinant TNF-, on ligature-induced periodontitis in rats

    JOURNAL OF PERIODONTAL RESEARCH, Issue 2 2003
    Rok Ga
    Proinflammatory cytokine tumor necrosis factor alpha (TNF-,) was found in inflamed periodontal tissues and many studies pointed to its significant role in development of periodontal disease. In this study, the influence of subcutaneously administered recombinant human TNF-, (rhTNF-,) on inflammatory reaction and periodontal breakdown in rats was analyzed during experimental periodontitis, induced by placing silk ligatures around the maxillary right second molar tooth. The rats were divided into two groups with five animals in each; the first group was infused subcutaneously with rhTNF-, via osmotic pumps for 2 weeks and the second group was infused with phosphate-buffered saline (PBS) in the same manner. Inflammatory reaction and periodontal breakdown was evaluated morphometrically on hematoxylin and eosin stained sections. Serum ionized calcium and inorganic phosphates were monitored colorimetrically. Serum calcium and phosphate levels were similar in rats receiving rhTNF-, and PBS. Ligation resulted in accelerated periodontal breakdown, while subcutaneous rhTNF-, administration by itself had no significant effect. Combined effect of subcutaneous rhTNF-, administration and ligation resulted in a significantly greater inflammatory reaction and periodontal breakdown then either treatment alone. We concluded that the subcutaneous administration of rhTNF-, accelerates the progression of experimental periodontitis in rats. [source]


    Role of nitric oxide in downregulation of cytochrome P450 1a1 and NADPH: Quinone oxidoreductase 1 by tumor necrosis factor-, and lipopolysaccharide

    JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2007
    Negar Gharavi
    Abstract We previously demonstrated that tumor necrosis factor alpha (TNF-,) and lipopolysaccharide (LPS) downregulate aryl hydrocarbon receptor (AhR)-regulated genes, such as cytochrome P450 1a1 (Cyp1a1) and NADPH: quinone oxidoreductase 1 (Nqo1) gene expression, yet the mechanisms involved remain unknown. The correlation between the inflammation-mediated suppression of AhR-regulated genes and the TNF-, or LPS-induced nitric oxide (NO) production especially in murine hepatoma Hepa 1c1c7 cells has been questioned; therefore we investigated whether NO is involved in the modulation of Cyp1a1 and Nqo1 by TNF-, or LPS in Hepa 1c1c7 cells. A significant dose-dependent increase in the inducible nitric oxide synthase (NOS2) expression and NO production were observed by various concentrations of TNF-, (1, 5, and 10 ng/mL) and LPS (1 and 5 µg/mL) which was completely inhibited by a NOS2 inhibitor, L-N6-(1-iminoethyl) lysine (L-NIL) (1 mM). Furthermore, TNF-, and LPS significantly induced NOS2 expression. Both TNF-, and LPS repressed the ,-naphthoflavone (,NF)-mediated induction of Cyp1a1 and Nqo1 at mRNA and activity levels. The downregulation of Cyp1a1, but not Nqo1, was significantly prevented by L-NIL. However, proxynitrite decomposer, iron tetrakis (N -methyl-4,-pyridyl) porphyrinato (FeTMPyP) (5 µM) did not affect TNF-,- and LPS-mediated downregulation of Cyp1a1 and Nqo1 at mRNA and activity levels. These results show that NO, but not peroxynitrite, may be involved in TNF-,- and LPS-mediated downregulation of Cyp1a1 without affecting the downregulation of Nqo1. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2795,2807, 2007 [source]


    Acute Ethanol Exposure Combined With Burn Injury Enhances IL-6 Levels in the Murine Ileum

    ALCOHOLISM, Issue 10 2007
    Michael T. Scalfani
    Background:, Recent studies suggest that ethanol use imposes a greater risk of trauma-associated intestinal injury than trauma alone. The initiating and regulatory factors for multiple organ dysfunction syndromes are not well defined, yet evidence points to the gut as a possible trigger of the systemic inflammatory cascade as well as a potential source of cytokines. In the current study, we hypothesized that ethanol administration would alter cytokine levels and intestinal infiltration by neutrophils within the ileum of mice exposed to burn injury (15% total body surface of dorsal skin). Methods:, Ileal samples were collected for histological assessment, myeloperoxidase quantitation and the protein presence of tumor necrosis factor alpha (TNF,), interleukin (IL-) 6, macrophage inflammatory protein-2 (MIP-2; CXCL2) and the anti-inflammatory cytokine, IL-10. Additional ileal tissue samples were examined for localization of the IL-6 immunoreactivity. Results:, We did not detect statistically significant cytokine/chemokine differences (MIP-2 and IL-10) between sham control and treatment conditions at either 2 or 24 hours. However, there was a significant decrease in TNF, at 24 hours in both burn injury alone and in combination with ethanol treatment conditions (p < 0.05). In addition, there was an increase in IL-6 levels at 24 hours in intestinal tissue obtained from mice subjected to a combination of acute ethanol and burn injury, compared to the mice receiving burn or sham injury (p < 0.001). Ileal homogenate increases in IL-6 at 24 hours were concurrent with decreased villus height in the ileum, but no discernable changes in neutrophil infiltration (myeloperoxidase activity levels) at either 2 or 24 hours. Additional immunocytochemical localization studies of ileal tissue revealed that there was a substantial increase of IL-6 in intestinal enterocytes subjected to both burn injury alone, or in combination with acute ethanol exposure. Conclusions:, The present study suggests that acute ethanol exposure combined with burn injury enhances levels of IL-6 protein in the ileum. The enhanced levels of ileal IL-6 are likely due to enterocyte production of the cytokine. [source]