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Type 2 Cytokines (type 2 + cytokine)
Selected AbstractsOPINION: Immunologic Abnormality of Intrahepatic Cholestasis of PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Hu Yayi Citation Yayi H, Danqing W, Shuyun L, Jicheng L. Immunologic Abnormality of Intrahepatic Cholestasis of Pregnancy. Am J Reprod Immunol 2010; 63: 267,273 Problem, Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy risk because of the possibility of pre-term delivery and sudden intrauterine fetal death. Its pathogenesis is still under discussion. Method of study, The analysis of the recent findings on the complex immunologic events that occur in ICP were performed. Results, In ICP, an increase of type 1 cytokine (TNF-,, IFN-,) associated with a decrease of type 2 cytokine (IL-4). The decreased production of the suppressor cytokine TGF-,2 may increase the type 1 cytokine. Fas appeared to be increased and FasL appeared to be decreased in syncytiotrophoblasts of ICP. The human leukocyte antigen gene (HLA-G, E) in extravillous trophoblasts of ICP were significantly decreased. Conclusion, Th1/Th2 cytokine balance and HLA play important roles in the tolerance and maintenance of pregnancy. ICP may be resulting from breach of the maternal fetal immune tolerance during pregnancy. [source] Effector CD8+ T cells in systemic sclerosis patients produce abnormally high levels of interleukin-13 associated with increased skin fibrosisARTHRITIS & RHEUMATISM, Issue 4 2009Patrizia Fuschiotti Objective T lymphocytes play an important role in systemic sclerosis (SSc), a connective tissue disease characterized by inflammation, fibrosis, and vascular damage. While their precise role and antigen specificity are unclear, T cell,derived cytokines likely contribute to the induction of fibrosis. The aim of this study was to establish the role of cytokine dysregulation by T cells in the pathogenesis of SSc. Methods To identify relationships between a specific cytokine, T cell subset, and the disease course, we studied a large cohort of patients with diffuse cutaneous SSc (dcSSc) or limited cutaneous SSc (lcSSc). Using Luminex analysis and intracellular cytokine staining, we analyzed the intrinsic ability of CD4+ and CD8+ T cell subsets to produce cytokines following in vitro activation. Results High levels of the profibrotic type 2 cytokine interleukin-13 (IL-13) were produced following activation of peripheral blood effector CD8+ T cells from SSc patients as compared with normal controls or with patients with rheumatoid arthritis. In contrast, CD4+ T cells showed a lower and more variable level of IL-13 production. This abnormality correlated with the extent of fibrosis and was more pronounced in dcSSc patients than in lcSSc patients. Conclusion Dysregulated IL-13 production by effector CD8+ T cells is important in the pathogenesis of SSc and is critical in the predisposition to more severe forms of cutaneous disease. Our study is the first to identify a specific T cell phenotype that correlates with disease severity in SSc and can be used as a marker of immune dysfunction in SSc and as a novel therapeutic target. [source] Cytokine and anti-cytokine therapy in asthma: ready for the clinic?CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2009D. Desai Summary Asthma is a common disease with an increasing prevalence worldwide. Up to 10% of these patients have asthma that is refractory to current therapy. This group have a disproportionate use of health care resources attributed to asthma, have significant morbidity and mortality and therefore represent an unmet clinical need. Asthma is a complex heterogeneous condition that is characterized by typical symptoms and disordered airway physiology set against a background of airway inflammation and remodelling. The inflammatory process underlying asthma is co-ordinated by a cytokine network. Modulating this network with biological therapy presents a new paradigm for asthma treatment. Clinical trials undertaken to date have underscored the complexity of the inflammatory profile and its relationship to the clinical features of the disease and have raised the importance of safety considerations related to these novel therapies. T helper type 2 cytokine blockade remains the most promising strategy, with anti-interleukin-5 reducing asthma exacerbations. Although anti-cytokine therapy is not yet ready for the clinic, the long-awaited possibility of new treatments for severe asthma is moving ever closer. [source] Interplay between T helper type 1 and type 2 cytokines and soluble major histocompatibility complex molecules: a paradigm in pregnancyIMMUNOLOGY, Issue 3 2002I. Athanassakis No abstract is available for this article. [source] Novel pharmacological approaches in the treatment of psoriasisJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2005V Schleyer ABSTRACT Progress in the understanding of psoriasis as a T-cell mediated inflammatory disease has led to the development of new immunomodulatory therapies. Currently the main focus is on the so-called biologics (or biological agents), including fusion proteins, monoclonal antibodies, cytokines and selective receptors. They mainly target single steps in the complex cascade of humoral and cellular inflammatory immunomechanisms that finally lead to the accelerated growth of epidermal and vascular cells in the psoriatic lesions. The most promising and advanced biological agents are discussed along with their influence on the critical pathophysiological steps in psoriasis, including depletion of T cells, blockade of initial T-cell activation and T-cell receptor (TCR) stimulation, blockade of costimulatory signals and T-cell proliferative signals as well as restoration of the T helper type 1 (Th1)/Th2 balance by diminishing type 1 cytokines and administration of type 2 cytokines. In addition to the biological agents, further development of ,classical' dermatological therapies, such as retinoids, or the discovery of new indications for non-dermatological agents contribute to the novel pharmacological approaches in the treatment of psoriasis. [source] Omega-3 fatty acid regulates inflammatory cytokine/mediator messenger RNA expression in Porphyromonas gingivalis -induced experimental periodontal diseaseMOLECULAR ORAL MICROBIOLOGY, Issue 4 2007L. Kesavalu Introduction:,Porphyromonas gingivalis is strongly implicated in the etiology of adult periodontitis by inducing inflammatory cytokines, resulting in gingival and periodontal tissue inflammation and alveolar bone resorption. This study tested the hypothesis that supplementing the diet with omega-3 fatty acid (,-3 FA; i.e. fish oil) would exert anti-inflammatory effects in the gingival tissues of P. gingivalis -infected rats. Methods:, Rats were fed either fish oil or corn oil diets ad libitum for 22 weeks and infected with P. gingivalis strain 381 or strain A7A1-28. After sacrifice, rat gingival tissues were excised and the RNA was isolated and analyzed for proinflammatory mediators [interleukin-1, (IL-1,), tumor necrosis factor-, (TNF-,), IL-6], T helper type 1 and type 2 cytokines [interferon-, (IFN-,), IL-4, IL-10), antioxidant enzymes [catalase (CAT), superoxide dismutase (SOD)], and genes critical for eicosanoid mediator production [cyclo-oxygenase-2 (COX-2), 5-lipoxygenase (5-LO)] by reverse transcription-polymerase chain reaction using rat-specific primers. Results:, Rats on the ,-3 FA diet exhibited decreased proinflammatory cytokine gene expression (IL-1,, TNF-,) and enhanced IFN-,, CAT and SOD messenger RNA expression compared to rats fed a corn oil diet, supporting a diet-induced modulation of host inflammatory reactions. Analyses of alveolar bone resorption in the rats related to gene expression profiles demonstrated significant positive correlations with IL-1,, IL-6 and COX-2 and negative correlations with CAT and SOD. Conclusion:, These findings suggest that diets enriched for ,-3 FA modulate the local gingival inflammatory milieu of the host following oral P. gingivalis infection, which impacts on alveolar bone resorption in rats. [source] T Helper Cell Cytokine Profiles in Preterm LaborAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2004Lisa M. Hollier Problem:, To compare concentrations of T-helper cell cytokines in women with preterm labor (PTL) to normal pregnancies. Method of study:, Fourteen women with PTL and 13 women with normal pregnancies from 24 to 34 weeks were enrolled in this pilot study. Peripheral blood mononuclear cells (PBMCs) and cervical secretions were collected. PBMCs were cultured and stimulated with mitogens. Culture supernatants and cervical secretions were assayed for type 1 (interferon- ,, IL-12) and type 2 cytokines (IL-4, IL-5, IL-10 and IL-13) using enzyme-linked immunosorbent assays. Results:, There were no intergroup differences in median cytokine concentrations in PBMC cultures, or in ratios of type 1/type 2 cytokines. In cervical secretions, the median concentration of IL-4 was significantly higher in control patients. Conclusions:, PTL patients appeared to have an altered T-helper cytokine balance in cervical secretions. Further study of the role of cytokines produced in the adaptive response appears warranted. [source] Increased frequency of intracellular interleukin (IL)-13 and IL-10, but not IL-4, expressing CD4+ and CD8+ peripheral T cells of patients with atopic dermatitisBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2002M. Aleksza Summary Background A number of studies exist demonstrating the increased expression of type 2 cytokines and decreased capacity to produce interferon-, (IFN-,) in peripheral blood mononuclear cells (PBMCs) of patients with atopic dermatitis (AD). Objectives To clarify the results of recent studies concerning the role of interleukin (IL)-4 and IL-13 in PBMCs of AD patients, we analysed the activation status of lymphocyte subpopulations. Methods We measured the intracellular expression and serum levels of certain type 1 and type 2 cytokines, using cell surface and intracellular cytokine staining, flow cytometry and enzyme-linked immunosorbent assay techniques. Results The frequency of IL-10 and IL-13 producing CD4+ and CD8+ T cells was significantly higher in patients with AD, while the frequency of IFN-, secreting helper and cytotoxic T cells was significantly lower in patients with AD than in control subjects. The serum levels of IL-10 and IL-13 were also significantly increased. There were no significant differences observed between the experimental groups in the frequency of IL-4 producing CD4+ and CD8+ cells. Conclusions This study demonstrates a type 2 cytokine production in the CD4+ and CD8+ T cells of AD patients, which is characterized by an elevated IL-13, but not by IL-4 secretion, and by an increased level of the immunoregulatory IL-10, which can contribute to a decrease in IFN-, expression. [source] Type 1 diabetes: can exercise impair the autoimmune event?CELL BIOCHEMISTRY AND FUNCTION, Issue 4 2008The L -arginine/glutamine coupling hypothesis Abstract Prevention of type 1 diabetes mellitus (T1DM) requires early intervention in the autoimmune process directed against ,-cells of the pancreatic islets of Langerhans, which is believed to result from a disorder of immunoregulation. According to this concept, a T-helper lymphocyte of type 1 (Th1) subset of T-lymphocytes and their cytokine products, the type 1 cytokines [e.g. interleukin 2 (IL-2), interferon gamma (IFN-,) and tumour necrosis factor beta (TNF-,)] prevail over immunoregulatory (anti-inflammatory) Th2 subset and its cytokine products, i.e. type 2 cytokines (e.g. IL-4, IL-6 and IL-10). This allows type 1 cytokines to initiate a cascade of immune/inflammatory processes in the islet (insulitis), culminating in ,-cell destruction. Activation of sympathetic-corticotropin-releasing hormone (CRH) axis by psychological stress induces specifically Th1 cell overactivity that determines enhanced glutamine utilization and consequent poor L -arginine supply for nitric oxide (NO)-assisted insulin secretion. This determines the shift of intraislet glutamate metabolism from the synthesis of glutathione (GSH) to that of L -arginine, leading to a redox imbalance that activates nuclear factor ,B exacerbating inflammation and NO-mediated cytotoxicity. Physical exercise is capable of inducing changes in the pattern of cytokine production and release towards type 2 class and to normalize the glutamine supply to the circulation, which reduces the need for glutamate, whose metabolic fate may be restored in the direction of GSH synthesis and antioxidant defence. Also, the 70-kDa heat shock protein (hsp70), which is immunoregulatory, may modulate exercise-induced anti-inflammation. In this work, we envisage how exercise can intervene in the mechanisms involved in the autoimmune process against ,-cells and how novel therapeutic approaches may be inferred from these observations. Copyright © 2008 John Wiley & Sons, Ltd. [source] Induction of insulin-like growth factor-I by interleukin-17F in bronchial epithelial cellsCLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2010M. Kawaguchi Summary Cite this as: M. Kawaguchi, J. Fujita, F. Kokubu, G. Ohara, S-K Huang, S. Matsukura, Y. Ishii, M. Adachi, H. Satoh and N. Hizawa, Clinical & Experimental Allergy, 2010 (40) 1036,1043. Background Increased expression of IL-17F has been noted in the airway of asthmatic patients, but its role in asthma has not been fully elucidated. Insulin-like growth factor-I (IGF-I) is known to be involved in airway remodelling and inflammation, while its regulatory mechanisms remain to be defined. Objective To further clarify the biological function of IL-17F, we investigated whether IL-17F is able to regulate the expression of IGF-I in bronchial epithelial cells. Methods Bronchial epithelial cells were stimulated with IL-17F in the presence or absence of T-helper type 2 cytokines. Various kinase inhibitors were added to the culture to identify the key signalling events leading to the expression of IGF-I, in conjunction with the use of short interfering RNAs (siRNAs) targeting mitogen- and stress-activated protein kinase (MSK) 1, p90 ribosomal S6 kinase (p90RSK), and cyclic AMP response element-binding protein (CREB). Results IL-17F significantly induced IGF-I gene and protein expression, and co-stimulation with IL-4 and IL-13 augmented its production. MAP kinase kinase (MEK) inhibitors and the Raf1 kinase inhibitor significantly inhibited IGF-I production, and the combination of PD98059 and Raf1 kinase inhibitor showed further inhibition. Overexpression of Raf1 and Ras dominant-negative mutants inhibited its expression. MSK1 inhibitors significantly blocked IL17F-induced IGF-I expression. Moreover, transfection of the siRNAs targeting MSK1, p90RSK, and CREB blocked its expression. Conclusions In bronchial epithelial cells, IL-17F is able to induce the expression of IGF-I via the Raf1,MEK1/2,ERK1/2,MSK1/p90RSK,CREB pathway in vitro. [source] Allergen-specific antibody and cytokine responses, mast cell reactivity and intestinal permeability upon oral challenge of sensitized and tolerized miceCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2010C. Perrier Summary Background Food allergy has reached an epidemic level in westernized countries and although central mechanisms have been described, the variability associated with genetic diversity underscores the still unresolved complexity of these disorders. Objective To develop models of food allergy and oral tolerance, both strictly induced by the intestinal route, and to compare antigen-specific responses. Methods BALB/c mice were mucosally sensitized to ovalbumin (OVA) in the presence of the mucosal adjuvant cholera toxin, or tolerized by intra-gastric administrations of OVA alone. Antibody titres and cytokines were determined by ELISA, and allergic status was determined through several physiologic parameters including decline in temperature, diarrhoea, mast cell degranulation and intestinal permeability. Results OVA-specific antibodies (IgE, IgGs and IgA in serum and feces) were produced in sensitized mice exclusively. Upon intra-gastric challenge with OVA, sensitized mice developed anaphylactic reactions associated with a decline of temperature, diarrhoea, degranulation of mast cells, which were only moderately recruited in the small intestine, and increased intestinal permeability. Cytokines produced by immune cells from sensitized mice included T-helper type 2 cytokines (IL-5, IL-13), but also IL-10, IFN-, and IL-17. In contrast, all markers of allergy were totally absent in tolerized animals, and yet the latter were protected from subsequent sensitization, demonstrating that oral tolerance took place efficiently. Conclusion This work allows for the first time an appropriate comparison between sensitized and tolerized BALB/c mice towards OVA. It highlights important differences from other models of allergy, and thus questions some of the generally accepted notions of allergic reactions, such as the protective role of IFN-,, the importance of antigen-specific secretory IgA and the role of mucosal mast cells in intestinal anaphylaxis. In addition, it suggests that IL-17 might be an effector cytokine in food allergy. Finally, it demonstrates that intestinal permeability towards the allergen is increased during challenge. Cite this as: C. Perrier, A.-C. Thierry, A. Mercenier and B. Corthésy, Clinical & Experimental Allergy, 2010 (40) 153,162. [source] Aggravation of bronchial eosinophilia in mice by nasal and bronchial exposure to Staphylococcus aureus enterotoxin BCLINICAL & EXPERIMENTAL ALLERGY, Issue 8 2006P. W. Hellings Summary Background The role of bacterial enterotoxins like Staphylococcus aureus enterotoxin B (SEB) in allergic asthma remains unknown. We used a mouse model of airway allergy to study the effects of nasal or bronchial contact with SEB on bronchial allergic inflammation. Methods The features of allergic asthma were induced in ovalbumin (OVA)-sensitized mice (days 1,13) by repeated exposures to nebulized OVA (days 33,37). Nasal or bronchial application of SEB was performed on three occasions (days 33,35,37), and the effects on bronchial inflammation, IgE titres and expression levels of mRNA for T helper type 2 cytokines and other inflammatory mediators were evaluated. Results Both nasal and bronchial SEB enhanced the allergen-induced bronchial inflammation, as reflected by more eosinophilic inflammation in the airway lumen and in bronchial tissue. Aggravation of experimental asthma correlated with higher expression of mRNA for IL-5, IL-4, IFN-,, IL-12 p40, eotaxin-1 and TGF-, in bronchi. In addition, nasal SEB elevated concentrations of IL-4, IL-5 and IFN-, in serum and bronchial SEB increased titres of OVA-specific and total IgE in serum. Conclusion Our data illustrate the potential of both nasal as well as bronchial SEB to aggravate several features of allergic asthma in a mouse model. [source] | ||||||||||||||||||||||