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Inflammatory Cytokine Production (inflammatory + cytokine_production)
Selected AbstractsInflammatory cytokine production by immunological and foreign body multinucleated giant cellsIMMUNOLOGY, Issue 3 2000R. Hernandez-Pando Summary Multinucleated giant cells (MGC) are a common feature of granulomas. The mechanism of their formation has been studied extensively, but their function has not been completely characterized. A new method for the in vivo production of MGC was developed involving subcutaneous injection of microscopic nitrocellulose particles with adsorbed mycobacterial antigens into the footpads of sensitized BALB/c mice (immune [I]-MGC), or by nitrocellulose administration to non-sensitized mice (foreign body [FB]-MGC). The development of granulomas with a highly enriched MGC population was observed 2 weeks after the nitrocellulose injection. MGC were larger with a greater number of nuclei in I-MGC than in FB-MGC. From days 7,28 after nitrocellulose administration, the production of interleukin-1, (IL-1,) and tumour necrosis factor-, (TNF-,) was demonstrated in both MGC types by in situ reverse transcription,polymerase chain reaction (RT,PCR) and immunohistochemistry. After 2 months, the MGC had ceased production of IL-1, and TNF-,, but the expression of transforming growth factor-, (TGF-,) was very high, occurring together with extensive fibrosis. These results suggest that MGC are an active source of inflammatory cytokines, which can contribute to the initiation, maintenance and down-regulation of granulomatous inflammation induced by immunological and inert substances. [source] Increased TLR responses in dendritic cells lacking the ITAM-containing adapters DAP12 and FcR,EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2008Ching-Liang Chu Dr. Abstract The inhibitory effect of DAP12 on macrophages has been revealed by examining myeloid cells from DAP12-deficient mice. In this report, we demonstrate that both DAP12 and the Fc,RI,-chain (FcR,) are required for negative regulation of TLR responses in bone marrow-derived dendritic cells (DC). Loss of both DAP12 and FcR, enhanced the pro-inflammatory cytokine production and maturation of DC after TLR stimulation, resulting in a greater percentage of DC that produced IL-12 p40, TNF, and IL-6, and expressed high levels of MHC class II, CD80, and CD86. Whereas DC lacking only DAP12 showed some increased TLR responses, those lacking only FcR, had a greater enhancement of maturation and cytokine production, though to a lesser extent than DC lacking both DAP12 and FcR,. Additionally, antigen-specific T cell proliferation was enhanced by DAP12,/,FcR,,/, DC relative to wild-type DC after maturation. Similar to DAP12,/,FcR,,/, DC, Syk-deficient DC also had increased inflammatory cytokine production, maturation, and antigen presentation. These results confirm the inhibitory effect of immunoreceptor tyrosine-based activation motif (ITAM) signaling in myeloid cells and show that DC and macrophages differ in their dependence on the ITAM-containing adapters DAP12 and FcR, for negative regulation of TLR signaling. [source] Modulation of dendritic cell phenotype and functionin an in vitro model of the intestinal epitheliumEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2006Matt Butler Abstract A network of dendritic cells (DC) can be detected in close proximity to the epithelial cells overlying Peyer's patches in the gut. Intestinal DC show distinct phenotypes as compared to DC from the systemic lymph nodes (relatively low MHC and costimulatory molecules and high IL-10 and TGF,) and may play a role in maintaining tolerance to enteric antigens. We show that a similar phenotype is induced in the presence of a polarised epithelial cell monolayer in vitro. Monocyte-derived DC were co-cultured with Caco-2 intestinal epithelial monolayers for 24,h. Co-culture resulted in DC with reduced expression of MHC class,II, CD86, and CD80, and poor T,cell stimulatory capacity. Cytokine profiles showed reduced levels of inflammatory cytokine production, and co-cultured DC were less sensitive to stimulation via Toll-like receptors (TLR2, 4, and 6) as a result of increased levels of autocrine TGF, production. However, phenotypic changes in co-cultured DC could not be blocked by removal of apoptotic cells or addition of anti-TGF, antibodies, suggesting that other soluble factors are involved in DC modulation. Thus, polarised epithelial cell monolayers create a ,tolerogenic' environment which modulates the activity of DC. These results highlight the regulatory importance of the epithelial microenvironment at mucosal surfaces. [source] Nuclear factor ,B decoy oligodeoxynucleotides prevent endotoxin-induced fatal liver failure in a murine modelHEPATOLOGY, Issue 2 2003Ichiro Ogushi Endotoxin syndrome is a systemic inflammatory response mediated by inflammatory cytokines. Nuclear factor ,B (NF-,B) is the dominant regulator of the production of these cytokines by inflammatory cells. The aim of this study was to assess the efficacy of in vivo transfer of synthetic double-stranded oligodeoxynucleotides (ODN) with high affinity against NF-,B (NF-,B/decoy/ODN) as a therapeutic strategy for treating endotoxin-induced fatal liver injury. Liver injury was induced by administration of lipopolysaccharide (LPS) to Propionibacterium acnes -primed BALB/C mice. NF-,B/decoy/ODN was transferred into the portal vein using a fusigenic liposome with hemagglutinating virus of Japan. NF-,B/decoy/ODN was preferentially transferred to Kupffer cells, and activation of NF-,B after the LPS challenge was suppressed, leading to decreased inflammatory cytokine production. As a result, the massive necrosis and hepatocyte apoptosis observed in the control mice was dramatically attenuated and the survival rate improved. In conclusion, NF-,B/decoy/ODN transfer in vivo effectively suppressed endotoxin-induced fatal liver injury in mice. [source] Sulfur mustard induced cytokine production and cell death: Investigating the potential roles of the p38, p53, and NF-,B signaling pathways with RNA interference,JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2010Albert L. Ruff Abstract Cutaneous and ocular injuries caused by sulfur mustard (SM; bis-(2-chloroethyl) sulfide) are characterized by severe inflammation and death of exposed cells. Given the known roles of p38MAPK and NF-,B in inflammatory cytokine production, and the known roles of NF-,B and p53 in cell fate, these pathways are of particular interest in the study of SM injury. In this study, we utilized inhibitory RNA (RNAi) targeted against p38,, the p50 subunit of NF-,B, or p53 to characterize their role in SM-induced inflammation and cell death in normal human epidermal keratinocytes (NHEK). Analysis of culture supernatant from 200 ,M SM-exposed cells showed that inflammatory cytokine production was inhibited by p38, RNAi but not by NF-,B p50 RNAi. These findings further support a critical role for p38 in SM-induced inflammatory cytokine production in NHEK and suggest that NF-,B may not play a role in the SM-induced inflammatory response of this cell type. Inhibition of NF-,B by p50 RNAi did, however, partially inhibit SM-induced cell death, suggesting a role for NF-,B in SM-induced apoptosis or necrosis. Interestingly, inhibition of p53 by RNAi potentiated SM-induced cell death, suggesting that the role of p53 in SM injury, may be complex and not simply prodeath. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:155,164, 2010; Published online inWiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20321 [source] Regulation of lipopolysaccharide-induced inflammatory response and endotoxemia by ,-arrestins,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2010Katie J. Porter ,-Arrestins are scaffolding proteins implicated as negative regulators of TLR4 signaling in macrophages and fibroblasts. Unexpectedly, we found that ,-arrestin-1 (,-arr-1) and -2 knockout (KO) mice are protected from TLR4-mediated endotoxic shock and lethality. To identify the potential mechanisms involved, we examined the plasma levels of inflammatory cytokines/chemokines in the wild-type (WT) and ,-arr-1 and -2 KO mice after lipopolysaccharide (LPS, a TLR4 ligand) injection. Consistent with lethality, LPS-induced inflammatory cytokine levels in the plasma were markedly decreased in both ,-arr-1 and -2 KO, compared to WT mice. To further explore the cellular mechanisms, we obtained splenocytes (separated into CD11b+ and CD11b, populations) from WT, ,-arr-1, and -2 KO mice and examined the effect of LPS on cytokine production. Similar to the in vivo observations, LPS-induced inflammatory cytokines were significantly blocked in both splenocyte populations from the ,-arr-2 KO compared to the WT mice. This effect in the ,-arr-1 KO mice, however, was restricted to the CD11b, splenocytes. Our studies further indicate that regulation of cytokine production by ,-arrestins is likely independent of MAPK and I,B,-NF,B pathways. Our results, however, suggest that LPS-induced chromatin modification is dependent on ,-arrestin levels and may be the underlying mechanistic basis for regulation of cytokine levels by ,-arrestins in vivo. Taken together, these results indicate that ,-arr-1 and -2 mediate LPS-induced cytokine secretion in a cell-type specific manner and that both ,-arrestins have overlapping but non-redundant roles in regulating inflammatory cytokine production and endotoxic shock in mice. J. Cell. Physiol. 225: 406,416, 2010. © 2010 Wiley-Liss, Inc. [source] Moderate Alcohol Intake in Humans Attenuates Monocyte Inflammatory Responses: Inhibition of Nuclear Regulatory Factor Kappa B and Induction of Interleukin 10ALCOHOLISM, Issue 1 2006Pranoti Mandrekar Background: In contrast to the deleterious effects of chronic excessive alcohol consumption on the liver and cardiovascular system, modest alcohol intake, such as 1 to 2 drinks per day, has benefits on cardiovascular mortality. Little is known about the length of time or the amounts of alcohol consumed that may cause alterations in inflammatory cells such as monocytes that are crucial to atherosclerotic vascular disease. Here, we determine in vivo effects of acute alcohol consumption on inflammatory cytokine production and nuclear regulatory factor ,B (NF- ,B) binding in human monocytes. Methods: Human blood monocytes were isolated by plastic adherence before and after acute alcohol consumption (2 ml vodka/kg body weight). Lipopolysaccharide (LPS)- and superantigen-induced tumor necrosis factor , (TNF ,), interleukin (IL)-1,, and IL-10 production were then determined in monocytes by ELISA. Nuclear regulatory factor- ,B activity of monocytes before and after alcohol consumption was estimated by electromobility shift assay and promoter-driven reporter activity. I,B, was determined by Western blotting in the cytoplasmic extracts. Results: Eighteen hours after moderate alcohol consumption, we found a significant reduction in monocyte production of inflammatory mediators, TNF- , and IL-1,, in response to LPS or staphylococcal enterotoxin B stimulation. Acute alcohol consumption inhibited LPS-induced DNA binding of the p65/p50 NF- ,B in monocytes that regulates the expression of both the TNF- , and the IL-1, genes. Consistent with this, acute alcohol treatment (25 mM) significantly reduced LPS-induced activation of an NF- ,B-driven reporter gene suggesting inhibition of this proinflammatory signaling pathway. Further, LPS-induced I,B, degradation was not affected by acute alcohol consumption indicating an I,B, -independent mechanism, as observed earlier in the in vitro acute alcohol studies. In contrast, monocyte production of the anti-inflammatory cytokine, IL-10, was augmented by acute alcohol intake. Conclusions: Our findings suggest that acute alcohol consumption has dual anti-inflammatory effects that involve augmentation of IL-10 and attenuation of monocyte inflammatory responses involving inhibition of NF- ,B. These mechanisms may contribute to the beneficial effects of moderate alcohol use on atherosclerosis. [source] Counter regulation of the high affinity IgE receptor, Fc,RI, on human airway dendritic cells by IL-4 and IL-10ALLERGY, Issue 11 2009A. Faith Background:, Immunoglobulin E is a signalling molecule within the environment of the respiratory tract, the high affinity receptor for which, Fc,RI, is expressed by dendritic cells (DC). Little is known, however, of the expression and function of Fc,RI on DC in the human respiratory tract. Methods:, CD1c+ DC were purified from surgically resected nasal turbinates of 11 atopic and 12 nonatopic patients with chronic rhinosinusitis. Expression of Fc,RI was determined by flow cytometry. Cytokine production by DC was determined by cytometric bead array. Results:, Expression of Fc,RI was significantly elevated on respiratory tract dendritic cells (RTDC) from atopic as compared to nonatopic patients. Activation of RTDC through Fc,RI induced production of the pro-inflammatory cytokines IL-6 and TNF-,, and the anti-inflammatory cytokine IL-10. The production of IL-6 and TNF-, was elevated in atopic compared to nonatopic patients studied. Conversely IL-10 production was elevated in nonatopic patients. Concomitant activation of Fc,RI and stimulation of RTDC with IL-4 inhibited production of IL-10 by RTDC. Neutralization experiments with anti-IL-10 Ab enhanced whereas addition of exogenous IL-10 to RTDC inhibited Fc,RI-mediated inflammatory cytokine production. Conclusion:, The function of Fc,RI on RTDC from patients with rhinosinusitis is susceptible to counter regulation by IL-4 and IL-10. [source] Salivary immunoglobulin A directed to oral microbial GroEL in patients with periodontitis and their potential protective roleMOLECULAR ORAL MICROBIOLOGY, Issue 5 2006M. Fukui The aim of this study was to identify salivary immunoglobulin A (IgA) directed to oral microbial GroEL in patients with periodontitis and to demonstrate their potential protective role through a reduction of inflammatory cytokine production induced by microbial GroEL. Using five different proteins belonging to the heat-shock protein 60 family, Western immunoblot analysis of salivary IgA from 63 subjects revealed immunoreactivities with Campylobacter rectus GroEL and Porphyromonas gingivalis GroEL in subjects with periodontitis (P < 0.05) compared to control subjects. Using the BIACORE 1000 to measure the salivary IgA titers directed towards C. rectus GroEL, high resonance unit (RU) values were observed in the saliva samples from patients with periodontitis (P < 0.01). Furthermore, the number of teeth with deep pocket depth (,5 mm) showed a high correlation coefficient with the RU value (r = 0.50, P < 0.01). C. rectus GroEL possessed the ability to stimulate the production of interleukin-6 by gingival fibroblasts. Interestingly, salivary IgA antibody directed to C. rectus GroEL caused a partial inhibition of interleukin-6 production. This study showed a relationship between high levels of salivary IgA directed to GroEL and periodontal disease severity. Although additional investigations are required, salivary IgA to GroEL may have a protective role by reducing the inflammatory response induced by GroEL derived from periodontopathogenic bacteria. [source] Amelioration of experimental autoimmune encephalomyelitis in Lewis rats treated with fucoidanPHYTOTHERAPY RESEARCH, Issue 3 2010Heechul Kim Abstract We examined whether fucoidan affected the clinical symptoms of experimental autoimmune encephalomyelitis (EAE) in rats. EAE was induced in Lewis rats that were immunized with guinea-pig myelin basic protein (MBP) and complete Freund's adjuvant. Fucoidan (50,mg/kg, daily) was administered to rats with EAE intraperitoneally, either in the EAE induction phase from either 1 day before immunization to day 7 post-immunization (PI), or the effector phase from day 8 to 14 PI, to test which phase of rat EAE is affected by fucoidan treatment. The onset, severity and duration of EAE paralysis in the fucoidan-treated group in the days 8,14 PI-treated rats, but not in days ,1,7 PI-treated rats, were significantly delayed, suppressed and reduced, respectively, compared with the vehicle-treated controls. Treatment with fucoidan reduced the encephalitogenic response and TNF-, production during EAE. Moreover, the clinical amelioration coincided with decreased infiltration of inflammatory cells in the EAE-affected spinal cord. The ameliorative effect of fucoidan on clinical paralysis in EAE-affected rats may be mediated, in part, by the suppression of the autoreactive T cell response and inflammatory cytokine production. Copyright © 2009 John Wiley & Sons, Ltd. [source] Identification of a potent immunostimulatory oligodeoxynucleotide from Streptococcus thermophilus lacZANIMAL SCIENCE JOURNAL, Issue 5 2009Takeshi SHIMOSATO ABSTRACT Immunostimulatory sequences of oligodeoxynucleotides (ODNs), such as CpG ODNs, are potent stimulators of innate immunity. Here, we identified a strong immunostimulatory CpG ODN, which we named MsST, from the lac Z gene of Streptococcus (S.) thermophilus ATCC19258, and we evaluated its immune functions. In in vitro studies, MsST had a similar ability as the murine prototype CpG ODN 1555 to induce inflammatory cytokine production and cell proliferation. In mouse splenocytes, MsST increased the number of CD80+CD11c+and CD86+CD11c+ dendritic cells and CD4+CD25+ regulatory T cells. We also analyzed the effects of MsST on the expression of regulatory cytokines by real-time quantitative PCR. MsST was more potent at inducing interleukin-10 expression than the ODN control 1612, indicating that MsST can augment the regulatory T cell response via Toll-like receptor 9, which plays an important role in suppressing T helper type 2 responses. These results suggest that S. thermophilus, whose genes include a strong Immunostimulatory sequence-ODN, is a good candidate for a starter culture to develop new physiologically functional foods and feeds. [source] Combined cell wall polysaccharide, mycotoxin and bacterial lipopolysaccharide exposure and inflammatory cytokine responsesAPMIS, Issue 7 2009LENE JOHANNESSEN Human exposure to environmental microbes occurs regularly. Microbial compounds may interact with each other to affect cellular responses. We hypothesized that interactions between microbial compounds could modulate inflammatory cytokine responses in vitro. We investigated monocyte production of the pro-inflammatory cytokine tumour necrosis factor-, (TNF-,) and the regulatory cytokine interleukin-10 (IL-10) after combined exposure to the fungal cell wall polysaccharide mannan and to the ,-glucan laminarin, the mycotoxin citrinin and bacterial lipopolysaccharide (LPS). Interactions between the cell wall microbial compounds were estimated statistically in a general linear mixed model. We found that LPS (100 ng/ml) and the used ,-glucan (up to 1000 ,g/ml) significantly interacted with each other to reduce TNF-, production. Mannan (up to 100 ,g/ml) did not interact with the ,-glucan, but interacted with LPS. IL-10 production was induced by LPS only. The mycotoxin citrinin did not induce cytokine production, but was toxic to the cells in a dose- and time-dependent manner. However, non-toxic doses of citrinin reduced LPS-induced IL-10 production while LPS-induced TNF-, production was not similarly reduced by citrinin. In conclusion, interactions between microbial compounds can modulate cellular inflammatory cytokine production and experimental investigations of one compound at a time could give misleading conclusions about these combined effects. [source] Fluoxetine and citalopram exhibit potent antiinflammatory activity in human and murine models of rheumatoid arthritis and inhibit toll-like receptorsARTHRITIS & RHEUMATISM, Issue 3 2010Sandra Sacre Objective Selective serotonin reuptake inhibitors (SSRIs), in addition to their antidepressant effects, have been reported to have antiinflammatory effects. The aim of this study was to assess the antiarthritic potential of 2 SSRIs, fluoxetine and citalopram, in murine collagen-induced arthritis (CIA) and in a human ex vivo disease model of rheumatoid arthritis (RA). Methods Following therapeutic administration of SSRIs, paw swelling was assessed and clinical scores were determined daily in DBA/1 mice with CIA. Joint architecture was examined histologically at the end of the treatment period. Cultures of human RA synovial membranes were treated with SSRIs, and cytokine production was measured. Toll-like receptor (TLR) function was examined in murine and human macrophages, human B cells, and human fibroblast-like synovial cells treated with SSRIs. Results Both SSRIs significantly inhibited disease progression in mice with CIA, with fluoxetine showing the greatest degree of efficacy at the clinical and histologic levels. In addition, both drugs significantly inhibited the spontaneous production of tumor necrosis factor, interleukin-6, and interferon-,,inducible protein 10 in human RA synovial membrane cultures. Fluoxetine and citalopram treatment also inhibited the signaling of TLRs 3, 7, 8, and 9, providing a potential mechanism for their antiinflammatory action. Conclusion Fluoxetine and citalopram treatment selectively inhibit endosomal TLR signaling, ameliorate disease in CIA, and suppress inflammatory cytokine production in human RA tissue. These data highlight the antiarthritic potential of the SSRI drug family and provide further evidence of the involvement of TLRs in the pathogenesis of RA. The SSRIs may provide a template for potential antiarthritic drug development. [source] Amphoteric liposomes enable systemic antigen-presenting cell,directed delivery of CD40 antisense and are therapeutically effective in experimental arthritisARTHRITIS & RHEUMATISM, Issue 4 2009Evangelos Andreakos Objective Mediation of RNA interference by oligonucleotides constitutes a powerful approach for the silencing of genes involved in the pathogenesis of inflammatory disease, but in vivo application of this technique requires effective delivery to immune cells and/or sites of inflammation. The aim of the present study was to develop a new carrier system to mediate systemic administration of oligonucleotides to rheumatoid arthritis (RA) joints, and to develop an antisense oligonucleotide (ASO),based approach to interfere with CD40,CD154 interactions in an experimental model of RA. Methods A novel liposomal carrier with amphoteric properties, termed Nov038, was developed and assessed for its ability to systemically deliver an ASO directed against CD40 (CD40-ASO). Male DBA/1 mice with collagen-induced arthritis were treated with Nov038-encapsulated CD40-ASO, and the effects of treatment on various parameters of disease activity, including clinical score, paw swelling, lymph node responses, and inflammatory cytokine production in the joints, were assessed. Results Nov038 was well tolerated, devoid of immune-stimulatory effects, and efficacious in mediating systemic oligonucleotide delivery to sites of inflammation. In mice with collagen-induced arthritis, Nov038 enabled the therapeutic administration of CD40-ASO and improved established disease, while unassisted CD40-ASO was ineffective, and anti,tumor necrosis factor , (anti-TNF,) treatment was less effective in this model. Nov038/CD40-ASO efficacy was attributed to its tropism for monocyte/macrophages and myeloid dendritic cells (DCs), resulting in rapid down-regulation of CD40, inhibition of DC antigen presentation, and reduction in collagen-specific T cell responses, as well as decreased levels of TNF,, interleukin-6 (IL-6), and IL-17 in arthritic joints. Conclusion Amphoteric liposomes represent a novel carrier concept for systemic and antigen-presenting cell,targeted oligonucleotide delivery with clinical applicability and numerous potential applications, including target validation in vivo and inflammatory disease therapeutics. Moreover, Nov038/CD40-ASO constitutes a potent alternative to monoclonal antibody,based approaches for interfering with CD40,CD40L interactions. [source] TNF Alpha,308 Genotype and Renin,Angiotensin System in Hemodialysis Patients: An Effect on Inflammatory Cytokine Levels?ARTIFICIAL ORGANS, Issue 2 2005Gultekin Genctoy Abstract:, Background: Renin,angiotensin system (RAS) was suggested to modulate inflammatory cytokine production. Angiotensin II was consistently shown to increase production of tumor necrosis factor alpha (TNF-,). However, inflammatory cytokines and RAS were modulated by genetic polymorphisms such as TNF-,,308 G > A and angiotensin-converting enzyme (ACE) I/D gene polymorphisms. The aim of this study was to investigate the effects of ACE and TNF-, genotypes on inflammatory cytokines in hemodialysis (HD) patients. Methods: ACE I/D and TNF-,,308 G > A genotypes, pre- and postdialysis plasma renin activity (PRA), serum ACE, interleukin-1 beta (IL-1,), and TNF-, levels were determined in 22 HD patients. Results: Predialysis serum ACE activity is correlated with TNF-, (r = 0.63; P = 0.01), and PRA was correlated with IL-1, levels (r = 0.49; P = 0.02). Pre/postdialysis IL-1, and TNF-, were similar in DD and II/ID ACE genotypes. Predialysis TNF-, and IL-1, (32.4 ± 5; 35.1 ± 4.2 vs. 28.1 ± 3.7; 26.5 ± 6.2 pg/mL; P < 0.05) and postdialysis TNF-, levels (30.4 ± 1.4 vs. 28.4 ± 0.82 pg/mL; P < 0.05) were significantly higher in TNF1/2 than TNF1/1 patients. Conclusion: ACE and TNF-,,308 G > A (1/2) gene polymorphisms may contribute to modulation of proinflammatory cytokine production and hence chronic inflammation in HD patients. [source] Interleukin 13 and inflammatory markers in human sepsis,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 6 2004N. Collighan Background: Interleukin (IL) 13 is an anti-inflammatory cytokine that reduces inflammatory cytokine production, and enhances monocyte survival and MHC class II and CD23 expression. The only report of IL-13 in human sepsis noted no increase in IL-13 concentration, in contrast to animal data. This study further examined the expression of IL-13 in relation to human sepsis. Methods: In a prospective observational study of 31 patients (24 men) with sepsis or septic shock, high-sensitivity enzyme-linked immunoabsorbent assay (ELISA) was used to quantify levels of tumour necrosis factor (TNF) , on admission, and on days 1, 3, 5 and 7 thereafter. IL-13 and IL-2 were assayed by standard ELISA, and HLA-DR on CD14-positive monocytes was measured by flow cytometry. Results: Twenty-three patients developed septic shock. Monocyte HLA-DR levels showed greater depression and a slower recovery in shocked than non-shocked patients. The serum IL-13 concentration was significantly higher in the shocked group from admission to day 3, but subsequently decreased to levels similar to those in the non-shocked group. IL-13 concentrations were higher in non-survivors. The TNF-, concentration was higher in those with septic shock than in those without. The TNF-, level correlated with IL-13 concentration (rS = 0·61, P = 0·002). The IL-13/TNF-, ratio was greater in patients with shock than those with sepsis only (P = 0·017). IL-2 was undetectable. Conclusion: In human sepsis and septic shock, IL-13 correlated with TNF-, expression, but its effect on HLA-DR class II molecules remains unclear. Copyright © 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] 2223: Carbon monoxide as a mediator in the retinaACTA OPHTHALMOLOGICA, Issue 2010C BUCOLO Purpose Carbonic monoxide (CO) is organic gas ubiquitously synthesized in mammalian tissues by enzyme that has constitutive and inducible forms. This gas is produced as metabolic end-product in specific cell life phases, and may acts as atypical neuronal messenger. Evidence has recently accumulated suggesting that CO may be cytoprotective because its bioactions, including inhibition of apoptosis, platelet aggregation, complement activation, and inflammatory cytokine production. CO appears to be important to counteract the cytotoxicity caused by excessive production of reactive oxygen (ROS) and nitrogen (RNS) species. Methods In vitro and in vivo models. Results Induction of heme oxygenase (HO)-1 by hemin has been found to prevent retinal cell death after ischemia provoked by ocular hypertension in rats. The LPS-induced expression of pro-inflammatory cytokines, in rat eye, is also inhibited by CO. Interestingly, drugs active as inhibitors of iNOS block CO-induced increases in cGMP in the retina.Drugs inhibiting NO formation by acting on iNOS activity have been found to potently reduce intraocular pressure. Studies from our lab showed that an increase of CO availability by hemin or carbon monoxide-releasing molecules lower the intraocular pressure, suggesting a suppress action of iNOS-derived NO production. Conclusion A better understanding of CO regulation may lead to new therapeutic options that are safer and more efficacious than currently available treatments for various sight-threatening eye diseases, such as retinal degenerations. [source] Successful granulocyte-colony stimulating factor treatment of Crohn's disease is associated with the appearance of circulating interleukin-10-producing T cells and increased lamina propria plasmacytoid dendritic cellsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2009P. J. Mannon Summary Granulocyte-colony stimulating factor (G-CSF) has proved to be a successful therapy for some patients with Crohn's disease. Given the known ability of G-CSF to exert anti-T helper 1 effects and to induce interleukin (IL)-10-secreting regulatory T cells, we studied whether clinical benefit from G-CSF therapy in active Crohn's disease was associated with decreased inflammatory cytokine production and/or increased regulatory responses. Crohn's patients were treated with G-CSF (5 µg/kg/day subcutaneously) for 4 weeks and changes in cell phenotype, cytokine production and dendritic cell subsets were measured in the peripheral blood and colonic mucosal biopsies using flow cytometry, enzyme-linked immunosorbent assay and immunocytochemistry. Crohn's patients who achieved a clinical response or remission based on the decrease in the Crohn's disease activity index differed from non-responding patients in several important ways: at the end of treatment, responding patients had significantly more CD4+ memory T cells producing IL-10 in the peripheral blood; they also had a greatly enhanced CD123+ plasmacytoid dendritic cell infiltration of the lamina propria. Interferon-, production capacity was not changed significantly except in non-responders, where it increased. These data show that clinical benefit from G-CSF treatment in Crohn's disease is accompanied by significant induction of IL-10 secreting T cells as well as increases in plasmacytoid dendritic cells in the lamina propria of the inflamed gut mucosa. [source] Psychosine-induced apoptosis and cytokine activation in immune peripheral cells of Krabbe patients,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2007Patrizia Formichi Globoid cell leukodystrophy or Krabbe disease (KD), is a hereditary disorder caused by galactosylceramidase deficiency. Progressive accumulation of psychosine is considered to be the critical pathogenetic mechanism of cell death in the Krabbe brain. Psychosine mechanism of action has not been fully elucidated. It seems to induce apoptosis in oligodendrocytes through a mitochondrial pathway and to up-regulate inflammatory cytokines production resulting in oligodendrocyte loss. Our aim was to evaluate the role of psychosine in apoptotic cell death and inflammatory response in a group of patients affected by KD using peripheral blood lymphocytes (PBLs) and peripheral blood mononuclear cells (PBMCs) as a cellular model. PBLs from KP and healthy controls were exposed to 20 µM psychosine and analysed by flow cytometry, agarose gel electrophoresis and fluorescence microscopy. Our results showed that psychosine induces apoptosis in PBLs through a mitochondrial pathway, but the apoptotic response was quite low especially KP. The role of psychosine in the up-regulation of cytokines (TNFalpha, IL8 and MCP1) has been evaluated by ELISA in PBMCs from KP and controls after stimulation with LPS and phytohemagglutinin. Both in basal condition and after LPS stimulation, cells from KP showed a significant increase in TNF-, production, reduced MCP1 levels and no modification in IL8. These results indicate that lymphomonocytes from KP had a basal proinflammatory pattern that was amplified by psychosine. In conclusion, the reduced apoptotic response and the atypical cytokine production observed in our experiments, suggest an involvement of inflammatory pattern in immune peripheral cells of KP. J. Cell. Physiol. 212:737,743, 2007. © 2007 Wiley-Liss, Inc. [source] | |||||||||||||