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Cytokine Interleukin (cytokine + interleukin)

Distribution by Scientific Domains
Medical Sciences86%
Life Sciences9%
Distribution within Medical Sciences
Immunology41%
Dermatology10%
8 Other Subdomains39%

Kinds of Cytokine Interleukin

  • proinflammatory cytokine interleukin
    		•

    Selected Abstracts

    Toll-like receptor 3 agonist poly(I:C)-induced antiviral response in human corneal epithelial cells

    IMMUNOLOGY, Issue 1 2006
    Ashok Kumar
    Summary The objective of this study was to examine the expression of Toll-like receptor 3 (TLR3) by human corneal epithelial cells (HCECs) and to determine whether exposure to the TLR3 agonist polyinosinic-polycytidylic acid [poly(I:C)]induces an antiviral response in these cells. Fluorescence-activated cell sorter (FACS) analysis revealed TLR3 to be constitutively expressed and distributed intracellularly in HCECs. Stimulation of HCECs with the TLR3 agonist poly(I:C) induced the activation of nuclear factor (NF)-,B and production of the proinflammatory cytokine interleukin (IL)-6 and the chemokine IL-8. Upon exposure to poly(I:C), HCECs initiated a potent antiviral response resulting in an increase of interferon (IFN)-, mRNA expression (7-fold). Poly(I:C) stimulation also up-regulated mRNA expression of the antiviral chemokine IFN-, inducible protein 10 (IP10), myxovirus resistance gene A and 2,,5,-oligoadenylate synthetase (5-, 10- and 9-fold, respectively), and secretion of IP10. These responses were also induced by exogenously added type 1 IFNs, but could not be blocked by pretreatment of the cells with anti-TLR3 monoclonal antibody, suggesting that the receptor was not expressed on the cell surface. Furthermore, incubation of HCECs with an endosomal acidification inhibitor, chloroquine, markedly inhibited poly(I:C)-mediated IFN-, expression in HCECs. These results suggest that corneal epithelial cells are important sentinels of the corneal innate immune system against viral infection, and that stimulation of TLR3 can induce the expression of key proinflammatory cytokines and chemokines and antiviral genes that help in the defence of the cornea against viral infection. [source]

    Regulation of epithelial cell cytokine responses by the ,3,1 integrin

    IMMUNOLOGY, Issue 2 2003
    Farah D. Lubin
    Summary Epithelial cells (EC) from various tissues can produce important cytokines and chemokines when stimulated by proinflammatory cytokines. These EC also receive signals from cell surface integrins, like the ,3,1 integrin, which is important in cell migration and wound healing of epithelial monolayers. However, little is known of the effect of integrin signals on cytokine responses by EC. Colonic Caco-2 cells treated with an anti-,3 integrin antibody prior to stimulation with the proinflammatory cytokine interleukin (IL)-1 yielded suppressed levels of mRNA and secreted IL-6, IL-8 and monocyte chemoattractant protein-1 as compared to cells treated with normal mouse immunoglobulin G. Lung A549 cells also showed a similar suppression of cytokine secretion. Likewise, treatment of the Caco-2 cells with the same antibody suppressed tumour necrosis factor-,-stimulated IL-6 secretion. Fab fragments of the anti-,3 integrin antibody did not induce the suppressive effect but did block the suppressive effect of the whole antibody suggesting that the effect of the antibody required cross-linking of the integrins. Finally, culture of the Caco-2 cells on laminin type 5 (the major ligand for this integrin) yielded depressed levels of IL-1-induced IL-6 secretion as compared to cells on laminin type 1. These data are the first indication that the ,3,1 integrin may cause a suppression of cytokine responses by EC which may be important in regulating the capacity of EC to respond during inflammation or wound healing. [source]

    Myxoid liposarcoma FUS-DDIT3 fusion oncogene induces C/EBP ,-mediated interleukin 6 expression

    INTERNATIONAL JOURNAL OF CANCER, Issue 4 2005
    Melker Göransson
    Abstract The myxoid/round cell liposarcoma oncogene FUS-DDIT3 is the result of a translocation derived gene fusion between the splicing factor FUS and DDIT3. In order to investigate the downstream targets of DDIT3, and the transforming effects of the FUS-DDIT3 fusion protein, we have introduced DDIT3-GFP and FUS-DDIT3-GFP constructs into a human fibrosarcoma cell line. The gene expression profiles of stable transfectants were compared to the original fibrosarcoma cell line by microarray analysis. We here report that the NF,B and C/EBP , controlled gene IL6 is upregulated in DDIT3- and FUS-DDIT3-expressing fibrosarcoma cell lines and in myxoid liposarcoma cell lines. Strong expression of the tumor associated multifunctional cytokine interleukin 6 was confirmed both at mRNA and protein level. Knockdown experiments using siRNA against CEBPB transcripts showed that the effect of FUS-DDIT3 on IL6 expression is C/EBP , dependent. Chromatin immunoprecipitation revealed direct interaction between the IL6 promoter and the C/EBP , protein. In addition, the effect of DDIT3 and FUS-DDIT3 on the expression of other acute phase genes was examined using real-time PCR. We demonstrate for the first time that DDIT3 and FUS-DDIT3 show opposite transcriptional regulation of IL8 and suggest that FUS-DDIT3 may affect the synergistic activation of promoters regulated by C/EBP ,,B. © 2005 Wiley-Liss, Inc. [source]

    Association of longevity with IL-10 ,1082 G/A and TNF-,,308 G/A polymorphisms

    INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 4 2010
    O. F. Khabour
    Summary Cytokines are crucial for the regulation of inflammation development in humans. Many studies have shown that variations in cytokine genes might play a role in determining human longevity. This study examined the changes in the gene pool relevant to the ,308 G/A polymorphism in the promoter region of the proinflammatory cytokine tumour necrosis factor (TNF)-, gene and the ,1082 G/A polymorphism in the promoter region of anti-inflammatory cytokine interleukin (IL)-10 gene with aging and survival selection occurs in the Jordanian population. IL-10 ,1028 G/A and TNF-,,308 G/A were genotyped in 119 randomly selected elderly subjects (41 women and 78 men) with a mean age of 90.2 years and young control subjects of 118 (46 women and 72 men) with a mean age of 31.9 years. No significant differences were found in the genotype and allele frequencies of TNF-, gene variants between the two groups (P > 0.05) while the IL-10 genotype and allele frequencies were significantly associated with longevity in men (P < 0.05) but not in women (P < 0.05). Thus, IL-10 ,1028 G/A polymorphism seems to play a role in the pathway to longevity in Jordanian men. [source]

    Analysis of cytokine genes polymorphism as markers for inhibitor development in haemophilia A

    INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 2 2010
    D. Chaves
    Summary Antibodies that block factor VIII (FVIII) activity appear in some haemophilia A patients treated with FVIII replacement therapy and severely impaired treatment. To date, the mechanisms that lead to this immune response are unknown. In this work, haplotypes of cytokine interleukin 10 (IL-10) gene have been associated with the presence of FVIII inhibitors in a group of Brazilian haemophilia A patients. The coexistence of a haplotype defining high IL-10 synthesis and one defining an intermediate production of cytokines is found to be associated with the group of patients who have a history of inhibitor development. Additionally, the coexistence of haplotypes defining high and low IL-10 syntheses is strongly associated with the group of negative inhibitors. These results have shown that the simple association considering only the presence or the absence of a haplotype and the development of inhibitors in haemophilia A is not sufficient. Data obtained in this work sustain the idea that the genetic studies may partly explain why only approximately 25% of haemophilia A patients develop FVIII inhibitors. Other genetic issues and details of the protein replacement therapy should be considered to measure the chances of a patient to develop anti-FVIII antibodies. [source]

    Serum levels of interleukin-10 and tumour necrosis factor- , in chronic periodontitis

    JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 10 2010
    Anna Passoja
    Passoja A, Puijola I, Knuuttila M, Niemelä O, Karttunen R, Raunio T, Tervonen T. Serum levels of interleukin-10 and tumour necrosis factor- , in chronic periodontitis. J Clin Periodontol 2010; 37: 881,887. doi: 10.1111/j.1600-051X.2010.01602.x Abstract Aims: To investigate, using a cross-sectional study design, whether the extent of periodontal inflammation associates with the serum levels of cytokine interleukin (IL)-10 and tumour necrosis factor (TNF)- , and their ratio. Material and Methods: The study group consisted of 61 subjects with chronic periodontitis and 30 control subjects with minimally inflamed periodontal tissues. Probing pocket depth (PD), bleeding on probing (BOP) and periodontal attachment level (AL) were measured. The serum IL-10 (pg/ml) and TNF- , (U/l) levels were analysed using enzyme-linked immunosorbent assays. After categorization of the subjects, associations between serum IL-10 and TNF- , levels and the extent of periodontal inflammation were studied using linear regression models adjusted for age, gender, body mass index and smoking. Results: A negative, partly dose-dependent association existed between the extent of BOP, PD4 mm and AL4 mm and serum IL-10 level. The subjects in the periodontitis group presented significantly higher serum TNF- , levels and their TNF- ,/IL-10 ratio was approximately threefold when compared with the ratio in the control group. Conclusions: The significantly higher serum TNF- ,/IL-10 ratio in the subjects with chronic periodontitis when compared with the ratio in the controls is indicative of a stronger systemic pro-inflammatory state in chronic periodontitis. [source]

    Anti-Inflammatory Effect of Cardiac Resynchronization Therapy

    PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 7 2006
    KNUT T. LAPPEGÅRD
    Background: Congestive heart failure (CHF) is associated with persistent immune activation. Medical therapy has been shown to exert only limited anti-inflammatory effects. Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in a subset of patients with heart failure, but it is not known whether this treatment affects the immune system as well. To test this hypothesis, eight patients with heart failure scheduled for CRT were investigated for immune activation before and 6 months after CRT treatment. Methods and Results: After 6 months, all patients had improved in NYHA-class and LVEF, and there was a statistically significant reduction in serum N-terminal pro brain natriuretic peptide (BNP). Furthermore, there was a statistically significant reduction in plasma levels of the chemokines monocyte chemoattractant protein 1 (MCP-1) and interleukin 8 (IL-8) and the cytokine interleukin 6 (IL-6). We observed no changes in the levels of interleukin 1, (IL-1,), tumor necrosis factor , (TNF-,), interleukin 10 (IL-10), or complement activation products. There was a significant correlation between changes in BNP and IL-6 (r = 0.74, P = 0.037). Conclusion: Although based upon a limited number of patients, this report indicates that CRT reduces peripheral markers of immune activation in patients with CHF. Further large scale studies are warranted to verify these findings. [source]

    TH1/TH2,3 Imbalance due to Cytokine-Producing NK, ,, T and NK-,, T Cells in Murine Pregnancy Decidua in Success or Failure of Pregnancy

    AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2001
    DAVID A. CLARK
    PROBLEM: Recurrent spontaneous abortion in DBA/2-mated CBA/J mice has been attributed to the production of Th1 cytokines (tumor necrosis factor [TNF]-, and interferon [IFN]-,) by asialoGM1+ natural killer (NK) cells and V,1.1,6.3+ T cells that infiltrate decidua by day 6.5, during the peri-implantation period. Abortions can be prevented by a second population of V,1.1,6.3 cells, which infiltrate on day 8.5 of gestation, and produce the Th2 cytokine interleukin (IL)-10 and Th3 cytokine transforming growth factor (TGF)-,2. In low abortion rate immunocompetent mice, most of the TGF-,2 is derived from ,, T cells. However, TGF-,2-producing cells are present in the decidua of pregnant severe combined immune deficient (SCID) mice, which lack ,, T cells. METHODS: The cells in day 13.5 decidua of CBA×DBA/2 matings and SCID×SCID matings were identified using flow cytometry and combined surface staining for ,, and/or asialoGM1, and intracellular cytokine staining for TNF-,, IFN-,, and TGF-,2,3. RESULTS: TGF-,2 and TNF-, were found in asialoGM1+ NK cells in SCID mouse decidua. In CBA×DBA/2 mated mice, two major and one minor subsets of cytokine-positive cells were identified: -,,-only T cells, double positive asialoGM1+,,+ (NK-,, T) cells, and a small number of asialoGM1+,,, NK-only cells. The NK-only and NK-,, T subsets showed a greater Th1/Th2,3 pattern of intracellular staining compared with the ,,-only subset. In the CBA×DBA/2 and SCID×SCID systems, Th1/Th2,3 ratios could not predict actual observed abortion rates but did correlate with susceptibility to abortions (if exposed to an additional stimulus such as stress). The known effect of in vivo administration of anti-asialoGM1 antibody on abortion rates within groups of mice exposed to such stresses could also be predicted. CONCLUSION: ,,+ cells in decidua (e.g. V,1+ cells which can recognize trophoblasts) differ based on the presence or absence of the NK marker-asialo-GM1. NK-,, T cells may be quite important in the Th1 response in early pregnancy that predisposes to abortions in CBA×DBA/2 matings, whereas ,, T-only cells appear to be protective. In pregnant SCID mice, the TNF-,+/TGF-,2+ NK population is greatly expanded. An activating stimulus (such as stress or endotoxin) appears to be as important in triggering abortions, as is the Th1/Th2,3 ratio at the feto,maternal interface. [source]

    Inflammatory stimuli from macrophages and cancer cells synergistically promote tumor growth and angiogenesis

    CANCER SCIENCE, Issue 12 2007
    Yusuke N. Kimura
    The focus of the present study was whether and how infiltrating macrophages play a role in angiogenesis and the growth of cancer cells in response to the inflammatory cytokine interleukin (IL)-1,. Lewis lung carcinoma cells overexpressing IL-1, grew faster and induced greater neovascularization than a low IL-1,-expressing counterpart in vivo. When macrophages were depleted using clodronate liposomes, both neovascularization and tumor growth were reduced in the IL-1,-expressing tumors. Co-cultivation of IL-1,-expressing cancer cells with macrophages synergistically augmented neovascularization and the migration of vascular endothelial cells. In these co-cultures, production of the angiogenic factors vascular endothelial growth factor-A and IL-8, monocyte chemoattractant protein-1, and matrix metalloproteinase-9 were increased markedly. The production of these factors, induced by IL-1,-stimulated lung cancer cells, was blocked by a nuclear factor (NF)-,B inhibitor, and also by the knockdown of p65 (NF-,B) and c-Jun using small interference RNA, suggesting involvement of the transcription factors NF-,B and AP-1. These results demonstrated that macrophages recruited into tumors by monocyte chemoattractant protein-1 and other chemokines could play a critical role in promoting tumor growth and angiogenesis, through interactions with cancer cells mediated by inflammatory stimuli. (Cancer Sci 2007; 98: 2009,2018) [source]

    Function of Siglec-8 on human eosinophils

    CLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 2004
    E. Nutku
    Summary Eosinophil recruitment and activation are regarded as central to the pathophysiology of allergic diseases, including asthma. An improved understanding of the mechanisms involved in these responses is therefore of great relevance to asthma pathogenesis and the development of new therapeutics. As part of ongoing efforts to discover novel eosinophil-specific molecules, we recently cloned Siglec-8 (formerly called sialoadhesin family member-2) from a human eosinophil cDNA library. Siglecs (sialic acid binding Ig-like lectins) are a family of transmembrane, I-type lectins characterized by an N-terminal V-set Ig domain that binds sialic acid. We now know that Siglec-8 is expressed only on human eosinophils, basophils and mast cells, giving it a unique expression pattern on effector cells of allergic disease. We have determined that in eosinophils, Siglec-8 exists in two isoforms, one of which contains two putative cytoplasmic tyrosine-based signalling motifs, including an ITIM (immunoreceptor tyrosine-based inhibitory motif) sequence. Because of the ITIM sequence, we hypothesized that Siglec-8 ligation would inhibit eosinophil functions. Initial studies found that incubation of eosinophils with Siglec-8 binding monoclonal antibodies under cross-linking conditions caused rapid and profound caspase-dependent apoptosis, and this response could not be rescued by the survival-promoting cytokine interleukin (IL)-5. In fact, IL-5 enhanced the ability of Siglec-8 cross-linking to induce eosinophil apoptosis. Activation via Siglec-8 could potentially be used to inhibit eosinophil survival in vivo, providing a novel strategy for reducing or inhibiting these cells in allergic and other diseases. [source]

    Differential immunomodulatory properties of Bifidobacterium logum strains: relevance to probiotic selection and clinical applications

    CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2007
    M. Medina
    Summary Modulation of host immunity is one of the proposed benefits of the consumption of probiotics. Nonetheless, comparative studies on the immunological properties that support the selection of strains of the same species for specific health benefits are limited. In this study, the ability of different strains of Bifidobacterium longum to induce cytokine production by peripheral blood mononuclear cells (PBMCs) has been evaluated. Live cells of all B. longum strains greatly stimulated regulatory cytokine interleukin (IL)-10 and proinflammatory cytokine tumour necrosis factor (TNF)-, production. Strains of the same species also induced specific cytokine patterns, suggesting that they could drive immune responses in different directions. The probiotic strain B. longum W11 stimulated strongly the production of T helper 1 (Th1) cytokines while B. longum NCIMB 8809 and BIF53 induced low levels of Th1 cytokines and high levels of IL-10. The effects of cell-surface components obtained by sonication of B. longum strains overall confirm the effects detected by stimulation of PBMCs with live cells, indicating that these components are important determinants of the immunomodulatory activity of B. longum. Genomic DNA of some strains stimulated the production of the Th1 and pro-inflammatory cytokines, interferon (IFN)-, and TNF-,, but not that of IL-10. None of the cell-free culture supernatants of the studied strains was able to induce TNF-, production, suggesting that the proinflammatory component of these strains is associated mainly with structural cell molecules. The results suggest that despite sharing certain features, some strains can perform a better functional role than others and their careful selection for therapeutic use is desirable. [source]

    Cytomegalovirus hyperimmunoglobulin: mechanisms in allo-immune response in vitro

    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2007
    K. Hoetzenecker
    Abstract Background Cytomegalovirus hyperimmunoglobulin (CMVIg) containing drugs are routinely administered in cardiac transplantation for prophylaxis against CMV disease. Yet little is known about their influence on transplant relevant immune functions. The aim of this study was to evaluate the effect of CMVIg on cellular immunity in in vitro experiments and to define their role in tolerance inducing mechanisms. Materials and methods/results CMVIg reduces proliferation in mixed lymphocyte reactions and anti-CD3 blastogenesis assays and is related to decreased production of immune modulating cytokines interleukin (IL)-2, interferonr (IFN,), IL-10. This antiproliferative effect is associated with a cell-cycle arrest in the G0/G1 phase and induction of apoptosis in CD8+ and natural killer cells. Co-incubation with CMVIg causes down-regulation of cell bound immunoglobulin and Fc,RIII surface expression on natural killer cells and leads to attenuation of antibody dependent cellular cytotoxicity effector functions. Conclusions We conclude that CMVIg induces immunological features on leukocytes in vitro that are known to be related to tolerance induction. Our observations extend the current concept of CMVIg as passive CMV prophylaxis to a therapeutic drug compound capable of reducing allogeneic immune response. [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]

    The Immune,Endocrine Interaction Varies with the Duration of the Inflammatory Process in Cardiac Surgery Patients

    JOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2000
    A. Roth-Isigkeit
    The present study investigated the perioperative course of cytokine release and hypothalamic-pituitary-adrenal (HPA) axis activation in relation to the duration of the inflammatory response in cardiac surgery patients. Twelve male patients scheduled for elective coronary artery bypass grafting surgery with cardiopulmonary bypass and general anaesthesia were divided into two study groups: group 1 (n=6) underwent surgery at 13.00 h±30 min, group 2 (n=6) at 08.30 h±50 min. Blood samples were collected preoperatively and up to the first postoperative day. Postoperatively, on the day of surgery, serum concentrations of the proinflammatory cytokines interleukin (IL)-6, IL-1, and tumour necrosis factor (TNF)- , were not significantly different between the two groups, while blood concentrations of cortisol, adrenocorticotrophic hormone (ACTH) and , -endorphin in group 2 patients were significantly higher than in group 1 patients. Postoperatively, on the day of surgery, ACTH and cortisol concentrations in group 1 patients were positively correlated to the blood concentrations of IL-1,, IL-6 and TNF- ,. By contrast, group 2 patients showed no significant relationship between cytokine release and activation of HPA axis at this time. Our results suggest that in patients undergoing cardiac surgery, the cytokine response is initiated before the HPA axis is fully activated. In the early postoperative period, cytokines appear to be involved in the activation of the HPA axis, while in the later postoperative period, high cortisol concentrations may inhibit the release of IL-6. [source]

    Estrogen-mediated immunomodulation involves reduced activation of effector T cells, potentiation of treg cells, and enhanced expression of the PD-1 costimulatory pathway

    JOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2006
    Magdalena J. Polanczyk
    Abstract Estrogen (E2)-induced immunomodulation involves dual effects on antigen-presenting cells (APC) and CD4+CD25+ regulatory T cells (Treg) but not a direct effect on effector T cells. In this report, we further investigated the effects of E2 on APC and Treg function. We found that E2 treatment in vivo strongly reduced recovery of APC from the peritoneal cavity and inhibited induction of the inflammatory cytokines interleukin (IL)-12 and interferon-, but enhanced secretion of IL-10. Moreover, E2-conditioned bone marrow-derived dendritic cells (BM-DC) could both enhance Treg activity and directly inhibit responder T cells in the absence of Treg cells. We examined whether this E2-induced inhibitory activity of BM-DC might involve costimulation through the recently described PD-1 pathway. Both E2 and pregnancy markedly enhanced PD-1 expression in several types of APC, including macrophages, B cells, and especially dendritic cells (DC). Similarly to E2-induced enhancement of FoxP3 expression and experimental autoimmune encephalomyelitis protection, E2-induced enhancement of PD-1+ cells was also mediated through estrogen receptor alpha (Esr1) in DC and macrophages but not in B cells. Based on antibody inhibition studies, PD-1 interaction with its ligands, PDL-1 and especially PDL-2, could mediate either positive or negative regulatory signaling in both mature and immature E2-conditioned DC, depending, respectively, on a relatively high (10:1) or low (1:1) ratio of T cells:BM-DC. These novel findings indicate that E2-induced immunomodulation is mediated in part through potentiation in BM-DC of the PD-1 costimulatory pathway. © 2006 Wiley-Liss, Inc. [source]

    From bench to bedside , translational research in psoriasis

    JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2010
    JC Prinz
    Abstract For many years, psoriasis was firmly believed to be a disease of epidermal keratinocytes, but now is attributed to a combination of genetic and environmental factors that promote a T-cell mediated immune response in the skin. Psoriasis is now understood to be a systemic T-cell mediated autoimmune disease with the innate immune system playing an important role. Progress in understanding the pathogenesis of psoriasis has shown that following a stimulus, dendritic and T cell activation leads to the release of cytokines, chemokines and growth factors that initiate the proliferation and altered differentiation of keratinocytes. These factors subsequently lead to continuous activation of T cells and antigen-presenting cells, particularly dendritic cells, within the psoriatic plaque. This vicious cycle of psoriasis, in which the cytokines interleukin 12 (IL-12) and IL-23 play a pivotal role, is a logical target for biological therapy. [source]

    Chemokine responses in schistosomal antigen-elicited granuloma formation,

    PARASITE IMMUNOLOGY, Issue 6 2002
    Bo-Chin Chiu
    Summary Host immune systems have evolved specialized responses to multicellular parasites. This is well represented by the type 2 granulomatous response to Schistosoma mansoni egg antigens, which is an eosinophil-rich inflammatory response mediated by Th2-associated cytokines. Using Ag-bead models of pulmonary granuloma formation in mice, we defined characteristic chemokine (CK) profiles in the granulomatous lungs. Our findings point to a role for C-C chemokine receptor-2 (CCR2) and CCR3 agonists such as monocyte chemotactic proteins (MCPs) 1/CCL2, 3/CCL7 and 5/CCL12 as important participants that are subject to regulation by Th2 cytokines interleukin (IL)-4 and IL-13. CCR4 and CCR8 agonists are also likely contributors. Analysis of CK receptor knockout mice revealed that CCR2 ligands (e.g. MCP-1 and 5) promoted early phase granuloma macrophage accumulation, whereas anti-MCP-3 (CCL7) antibody treatment abrogated eosinophil recruitment. CCR8 knockout mice also demonstrated impaired eosinophil recruitment but this appeared to be related to impaired Th2 cell function. Transcript analysis of CD4+ T cells generated during schistosome granuloma formation failed to show biased CCR8 expression but, having a more limited receptor repertoire, these cells were likely more dependent on CCR8 ligands. Together, these studies indicate an intricate involvement of chemokines in various stages and aspects of schistosomal egg Ag-elicited granuloma formation. [source]

    Erythema Toxicum Neonatorum: An Immunohistochemical Analysis

    PEDIATRIC DERMATOLOGY, Issue 3 2001
    Giovanna Marchini M.D., Ph.D.
    The recruitment of leukocytes to tissues implicates the involvement of adhesion molecules, cytokines, and chemokines. We therefore performed immunohistochemistry on punch biopsy specimens from cutaneous lesions of ten 1-day-old infants with erythema toxicum using specific monoclonal antibodies directed against a variety of adhesion molecules, cytokines, chemokines, and cell type-specific membrane markers. Biopsy specimens of noninflamed skin from four matched newborns and four adults served as controls. The immunohistologic features of erythema toxicum in all 10 infants included a strong staining of the adhesion molecule E-selectin in the vessel wall and the presence of numerous inflammatory cells that were identified as dendritic cells (CD1a, CD83, HLA-DR, CD40, and ICAM-1 positive), eosinophils (EG2 positive), neutrophils (CD15 positive), macrophages (CD14, CD68, and Mac387 positive), and E-selectin-expressing cells. Furthermore, the lesions showed a high incidence of the proinflammatory cytokines interleukin (IL)-1, and IL-1, and of the chemokines IL-8 and eotaxin. This immunologic activity was reduced or absent in noninflamed skin from newborn controls and adults. We conclude that there is an accumulation and activation of immune cells in the lesions of erythema toxicum, also present in noninflamed skin of 1-day-old infants, but to a lower level. The physiologic significance of the rash remains to be elucidated. [source]

    ORIGINAL ARTICLE: The Role of Cytokine Expression in Different Subgroups of Subfertile Men

    AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2009
    Srividya Seshadri
    Problem, The aim of this study was to evaluate the levels of seminal plasma cytokines interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin 11 (IL-11), interleukin 12 (IL-12), tumour necrosis factor alpha (TNF-,) and interferon gamma (IFN-,) in male subfertility. Method of study, A total of 73 male partners of an infertile couple attending a regional andrology unit were recruited into this prospective study and subdivided into the various groups based on semen analysis. Concentrations of cytokines such as IL-6, IL-8, IL-10, IL-11, IL-12, TNF-, and IFN-, in the seminal plasma were determined using enzyme linked immunosorbent assay (ELISA). Results, Significant higher concentrations (P < 0.05) of IL-6 in the mild and severe oligospermic group, IL-8 and IL-10 in the asthenospermic group and IL-6, IL-10, TNF-, and IFN-, in the obstructed azoospermic group were determined. IL-10 concentrations correlated significantly with other cytokines in the obstructed azoospermic group and the asthenospermic group. Conclusion, Our study confirms that cytokines rarely act in isolation, but rather in a network of other cytokines and may affect sperm function directly or indirectly. The presence of increased levels of cytokines in the obstructed azoospermic group suggests that the cytokines may not originate from the testis. [source]

    Proinflammatory action of the antiinflammatory drug infliximab in tumor necrosis factor receptor,associated periodic syndrome

    ARTHRITIS & RHEUMATISM, Issue 2 2009
    Belinda Nedjai
    Objective Tumor necrosis factor receptor (TNFR),associated periodic syndrome (TRAPS) is an autosomal-dominant autoinflammatory condition caused by mutations in the TNFRSF1A gene. Unlike other autoinflammatory diseases in which anti-TNF therapy is largely a successful treatment option, therapy with the anti-TNF drug infliximab is often ineffective in patients with TRAPS. Moreover, in certain cases, infliximab actually triggers severe episodes of inflammation. The aim of this study was to elucidate the mechanisms underlying such a reaction. Methods Peripheral blood mononuclear cells (PBMCs) were obtained from patients with TRAPS. Both caspase 3 activity and NF-,B subunit activity were determined by enzyme-linked immunosorbent assay. Cytokine secretion was assessed using a specific customized human multiplex bead immunoassay kit. Results Unlike findings in controls, cells from a family of 9 patients, all of whom carried the T50M mutation in TNFRSF1A, failed to respond to infliximab through proapoptotic induction of caspase 3 activity. Instead, we observed enhanced antiapoptotic c-Rel subunit activity, accompanied by a significant increase in secretion of the proinflammatory cytokines interleukin- 1, (IL-1,), IL-1 receptor, IL-6, IL-8, and IL-12. Conclusion Altered extracellular conformation of TNFRI, resulting from the T50M mutation in TNFRSF1A, results in failure of PBMCs to induce an apoptotic response to infliximab. We hypothesize that failure to shed infliximab-bound TNF/TNFRI from the cell surface of cells from patients with the T50M mutation triggers c-Rel activation, and that this leads to a marked increase in cytokine secretion and an increased proinflammatory response. In light of these findings, we strongly advise caution when prescribing infliximab as anti-TNF therapy to patients with TRAPS. [source]

    ESX-1-dependent cytolysis in lysosome secretion and inflammasome activation during mycobacterial infection

    CELLULAR MICROBIOLOGY, Issue 9 2008
    Ingrid C. Koo
    Summary Exocytosis of lysosomes from macrophages has been described as a response to microbial cytotoxins and haemolysins, as well as for releasing pro-inflammatory cytokines interleukin (IL)-1, and IL-18 during inflammasome activation. The mycobacterial ESX-1 secretion system, encoded in part by the Region of Difference-1, is a virulence factor necessary for phagosome escape and host cell lysis by a contact-dependent haemolysin in Mycobacterium marinum. Here we show that ESX-1 from M. marinum and M. tuberculosis is required for Ca2+ -dependent induction of lysosome secretion from macrophages. Mycobacteria-induced lysosome secretion was concurrent to release of IL-1, and IL-18, dependent on phagocytosis of bacteria containing ESX-1. Synthesis but not release of IL-1, and IL-18 occurred in response to dead bacilli and bacteria lacking ESX-1, indicating that only cytokine release was regulated by ESX-1. Release of these cytokines and exocytosis of lysosomes were independent of intracellular mycobacterial growth, yet correlated with mycobacteria-encoded haemolytic activity, demonstrating a parallel pathway for the two responses. We further identified inflammasome components caspase-1, ASC and NALP3, but not Ipaf, required for release of IL-1, and IL-18. Collectively, these results reveal a role for ESX-1 in triggering secretion of lysosomes, as well as release of IL-1, and IL-18 during mycobacteria infection. [source]

    TOCOTRIENOL OFFERS BETTER PROTECTION THAN TOCOPHEROL FROM FREE RADICAL-INDUCED DAMAGE OF RAT BONE

    CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2005
    NS Ahmad
    SUMMARY 1.,Free radicals generated by ferric nitrilotriacetate (FeNTA) can activate osteoclastic activity and this is associated with elevation of the bone resorbing cytokines interleukin (IL)-1 and IL-6. In the present study, we investigated the effects of 2 mg/kg FeNTA (2 mg iron/kg) on the levels of serum IL-1 and IL-6 with or without supplementation with a palm oil tocotrienol mixture or ,-tocopherol acetate in Wistar rats. 2.,The FeNTA was found to elevate levels of IL-1 and IL-6. Only the palm oil tocotrienol mixture at doses of 60 and 100 mg/kg was able to prevent FeNTA-induced increases in IL-1 (P < 0.01). Both the palm oil tocotrienol mixture and ,-tocopherol acetate, at doses of 30, 60 and 100 mg/kg, were able to reduce FeNTA-induced increases in IL-6 (P < 0.05). Therefore, the palm oil tocotrienol mixture was better than pure ,-tocopherol acetate in protecting bone against FeNTA (free radical)-induced elevation of bone-resorbing cytokines. 3.,Supplementation with the palm oil tocotrienol mixture or ,-tocopherol acetate at 100 mg/kg restored the reduction in serum osteocalcin levels due to ageing, as seen in the saline (control) group (P < 0.05). All doses of the palm oil tocotrienol mixture decreased urine deoxypyridinoline cross-link (DPD) significantly compared with the control group, whereas a trend for decreased urine DPD was only seen for doses of 60 mg/kg onwards of ,-tocopherol acetate (P < 0.05). 4.,Bone histomorphometric analyses have shown that FeNTA injections significantly lowered mean osteoblast number (P < 0.001) and the bone formation rate (P < 0.001), but raised osteoclast number (P < 0.05) and the ratio of eroded surface/bone surface (P < 0.001) compared with the saline (control) group. Supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent all these FeNTA-induced changes, but a similar dose of ,-tocopherol acetate was found to be effective only for mean osteoclast number. Injections of FeNTA were also shown to reduce trabecular bone volume (P < 0.001) and trabecular thickness (P < 0.05), whereas only supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent these FeNTA-induced changes. [source]