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Th2-type Cytokines (th2-type + cytokine)
Selected AbstractsIn vivo expression of signal transducer and activator of transcription factor 6 (STAT6) in nasal mucosa from atopic allergic rhinitis: effect of topical corticosteroidsCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2000Ghaffar Background The allergen-induced late nasal response is associated with a high local expression of interleukin (IL) -4, a TH2-type cytokine implicated in immunoglobulin (Ig) E production, tissue eosinophilia and other events considered to be relevant to allergic inflammation. Interaction of IL-4 with its receptor activates at least two distinct signalling pathways that culminate in the transcription of specific target genes. One pathway involves the activation of a transcription factor termed signal transducer and activator of transcription factor 6 (STAT6). Objective To investigate the expression of STAT6 in the allergen-induced late nasal response and to examine the effect of local steroid treatment on STAT6 expression. Methods Inferior turbinate biopsies were obtained from subjects with allergic rhinitis out of the allergen season. Subjects were then randomized into topical steroid- (n = 6) and placebo-treated (n = 6) groups in a double-blind fashion. After a 6-week treatment period, a second nasal biopsy was performed 24 h after local challenge with allergen. STAT6 immunoreactivity was examined in biopsy specimens by immunocytochemistry using a specific monoclonal antibody. Numbers of inflammatory cells (CD3+ T cells and MBP+ eosinophils) and IL-4 mRNA+ cells were investigated by immunocytochemistry and in situ hybridization, respectively. Results STAT6 immunoreactivity was detected in all biopsies studied and localized predominantly to inflammatory tissue of the nasal mucosa. After allergen challenge, expression of STAT6 was markedly increased in placebo-treated patients (P < 0.01). By confocal microscopy, STAT6 was localized to the cytoplasm and the nucleus of positively-staining cells. The allergen-induced increase in STAT6 immunoreactive cells was not observed in the steroid-treated patients. The change in STAT6 immunoreactivity after allergen challenge correlated significantly with the change in numbers IL-4 mRNA+ cells (r = 0.74, P = 0.006) and CD3+ T cells (r = 0.76, P = 0.004), but not MBP+ eosinophils. Conclusion This study provides the first evidence of increased STAT6 expression in vivo in human allergic inflammation. The results support a role for STAT6 and IL-4 in the pathogenesis of late nasal response and show that decreases in STAT6 expression parallel the reduction in IL-4 expression that occurs with topical steroid treatment. [source] Mitoxantrone treatment in multiple sclerosis induces TH2-type cytokinesACTA NEUROLOGICA SCANDINAVICA, Issue 4 2010A. Vogelgesang Vogelgesang A, Rosenberg S, Skrzipek S, Bröker BM, Dressel A. Mitoxantrone treatment in multiple sclerosis induces TH2-type cytokines. Acta Neurol Scand: 2010: 122: 237,243. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives,,, Mitoxantrone is a cytotoxic drug with immune modulatory properties used in the treatment of progressive forms of multiple sclerosis (MS). We explored the effect of mitoxantrone treatment in MS patients on cytokine patterns induced in peripheral blood mononuclear cells (PBMC) and T-cell subsets ex vivo. Materials and methods,,, Blood was obtained before mitoxantrone infusion and 6, 12 and 18 days thereafter. Proliferation and prototypic TH1-, TH17- and TH2-type cytokines were determined following in vitro stimulation of PBMC, CD4+ and CD8+ T cells. In addition, a patient cohort receiving its first mitoxantrone treatment was cross-sectionally compared with a cohort of patients with more than 1 year of treatment. Results,,, Mitoxantrone treatment increased the ex vivo production of the TH2 cytokines interleukin-4 (IL-4; P < 0.05) and IL-5 (P < 0.001) in phytohemagglutinin-stimulated CD4+ T cells within 18 days of treatment. The cross-sectional study revealed that long-term treatment with mitoxantrone increased the inducibility of IL-4 and IL-5 secretion by PBMCs and CD4+ T cells even further. No significant changes were observed for interferon-,, tumour necrosis factor-,, IL-17 and IL-10. Mitoxantrone did not alter the proliferative capacity of ex vivo -stimulated T cells. Conclusion,,, Mitoxantrone treatment in MS enhances the inducibility of TH2-type cytokines, which may contribute to its beneficial effects in MS. [source] Immunohistochemical analysis of Th1/Th2 cytokine profiles and androgen receptor expression in the pathogenesis of nifedipine-induced gingival overgrowthJOURNAL OF PERIODONTAL RESEARCH, Issue 4 2003W-T. Huang Background:, Numerous studies have demonstrated that gingival overgrowth may be associated with androgen and cytokine expression in tissues. Objectives:, The aim of this study was to compare the expression of androgen receptor-presenting cells (AR+ cells) and Th1/Th2 cytokine [Th1: interleukin (IL)-2, interferon-, (IFN-,); Th2: IL-4, IL-10, IL-13] expression cells in tissue sections of patients with gingival overgrowth. Materials and methods:, Tissue samples were collected from patients with healthy periodontium (H group), adult periodontitis (P group), surgically extracted teeth (S group), and nifedipine-induced gingival overgrowth (NIGO group). The clinical periodontal parameters of pocket depth (PD), bleeding on probing (BOP), and plaque control record (PCR) were measured around selected sample teeth. Gingival biopsies were further processed by immunohistochemical staining method. The expressions of cells positive for AR, IL-2, IFN-,, IL-4, IL-10, and IL-13 were counted by predetermined semiquantitative methods. Results:, Our results indicated that AR, IL-2, IFN-,, IL-4, IL-10, and IL-13 were intensively expressed in the nuclei of inflammatory cells and fibroblasts of gingival connective tissue. Stronger expressions of AR, IL-2, and IFN-, were found in the NIGO group. The AR+ cells/0.01 mm2 in gingival fibroblasts were significantly higher in the NIGO group (80.2 ± 10.7) than those of the periodontitis group (52.5 ± 11.8) and control group (37.4 ± 11.3) (P < 0.05). The cytokine expression of the NIGO group showed a trend towards Th1-type expression (IL-2; P = 0.0001). In the surgically extracted tooth group, a stronger expression of Th2-type cytokine (IL-4, Il-10, IL-13; P < 0.05) was found in inflammatory cells. In a comparison of the IL-2/IL-4-labeled cell ratio of the four groups, a descending sequence was discovered as NIGO group (0.92 ± 0.97) > H group (0.81 ± 0.61) > P group (0.77 ± 0.82) > S group (0.58 ± 1.77). Conclusions:, Our data support the following: (i) taking nifedipine may elevate the expression of AR in susceptible oral tissue, e.g. gingiva; (ii) the cytokine profile of T-cells in NIGO tissue indicates a trend preferentially towards Th1 activity; and (iii) elevation of AR expression cells and prominent Th1 cytokine-labeled cells are two significant factors in the pathogenesis of NIGO. [source] IL-5-induced airway eosinophilia , the key to asthma?IMMUNOLOGICAL REVIEWS, Issue 1 2001Eckard Hamelmann Summary: Bronchial asthma is a chronic inflammatory airway disease defined by reversible airway obstruction and non-specific airway hyper-responsiveness (AHR). Although profound insights have been made into the pathophysiology of asthma, the exact mechanisms inducing and regulating the disease are still not fully understood. Yet, it is generally accepted that the pathological changes in asthma are induced by a chronic inflammatory process which is characterized by infiltration of the bronchial mucosa with lymphocytes and eosinophils, increased mucus production and submucosal edema. There is increasing evidence that an imbalance in the T-helper (Th) cell response of genetically predisposed individuals to common environmental antigens plays a pivotal role in the pathogenesis of allergic bronchial asthma and other atopic disorders. Following allergic sensitization, T cells from atopic patients tend to produce elevated levels of Th2-type cytokines, especially interleukin (IL)-4, IL-13, IL-5 and IL-6, which induce and regulate IgE production and eosinophil airway infiltration. In this review, the role of Th2-type cytokines, IgE and airway eosinophils in the induction of airway inflammation and AHR is discussed, and animal studies of asthma and AHR, mainly in rodents will be considered. A better understanding of the underlying mechanisms leading to asthma pathology may yield more specific immunological strategies for the treatment of this disease which is increasing worldwide. I thank the many colleagues in the laboratory of Dr. E. W. Gelfand, National Jewish Research Center, Denver CO, USA, for continuous support and encouragement. E.H. is a fellow of the Deutsche Forschungsgemeinschaft (DFG Ha 2162/1-1 and 2-1). [source] Changes in Cytokine Production During and After Normal PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2000YUKI SHIMAOKA PROBLEM: The systemic T helper 1/T helper 2 (Th1/Th2) cytokine balance during normal human pregnancy is controversial, and observations about the balance in the postpartum period have only been reported for up to 3 months. METHOD: Whole-blood, from 83 healthy pregnant women, 80 healthy postpartum women, and 31 healthy non-pregnant women was stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, and the levels of cytokines in the supernatant were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The production of all measured cytokines decreased during pregnancy, especially in the second trimester. After delivery, interferon-, (IFN-,) and interleukin-2 (IL-2) increased from 2 to 11 months postpartum, and IL-4 increased from 6 to 11 months postpartum. CONCLUSIONS: These data indicate that 1) decreases in production of both Th1- and Th2-type cytokines during pregnancy may be related to the pregnancy-induced amelioration of autoimmune diseases; 2) increases in production of both Th1- and Th2-type cytokines in the postpartum period may be related to the postpartum aggravation of autoimmune diseases. [source] Induction of eotaxin production by interleukin-4, interleukin-13 and lipopolysaccharide by nasal fibroblastsCLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2004M. Nonaka Summary Background There is growing evidence that eotaxin is a key mediator in the development of tissue eosinophilia. Fibroblasts are a major source of eotaxin. The severity of diseases with eosinophilic inflammation like nasal polyposis, atopic dermatitis and asthma, where Th2-type cytokines (IL-4 and IL-13) and TGF-, are expressed locally, was shown to correlate with bacterial factors such as lipopolysaccharide (LPS) rather than allergen. Objective We examined eotaxin production by nasal fibroblasts stimulated with IL-4 or IL-13 alone or in combination with LPS, and the effect of TGF-,1 on it. Moreover, we compared the magnitude of eotaxin produced by nasal fibroblasts with that produced by lung or skin fibroblasts. Methods Fibroblast lines were established from human biopsy tissue. The expression of eotaxin mRNA was evaluated by RT-PCR. The amount of eotaxin in the supernatants was measured by ELISA. Results IL-4, but not IL-13, synergized with LPS to produce eotaxin in a dose- and time-dependent manner. Sequential treatment of nasal fibroblasts with IL-4 and LPS did not have any effect. But when IL-4 and LPS were added together, synergy for eotaxin production was observed. Moreover, this synergy was observed in nasal and skin fibroblasts, but not in lung fibroblasts. The production of eotaxin by IL-4 and LPS was modulated by TGF-,1. Conclusion These results suggest that a co-stimulus like LPS is necessary for IL-4 to make a strong induction of eotaxin in eosinophilic inflammations such as nasal polyposis. Modulation by TGF-,1 may have important implications for the development of eosinophilic inflammation. [source] | ||||||||||