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Th2-associated Cytokines (th2-associated + cytokine)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Neutropenia alters lung cytokine production in mice and reduces their susceptibility to pulmonary cryptococcosis

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2003

Abstract Neutrophils are generally considered to contribute to host defense through their potent microbicidal activity. However, there is accumulating evidence that neutrophils also have an important regulatory role in establishing the balance of Th1 and Th2 responses. This study investigated the role of neutrophils in defense against pulmonary Cryptococcus neoformans infection using neutrophil-depleted BALB/c mice generated by administering mAb RB6,8C5. Neutropenic mice with pulmonary infection survived significantly longer than control mice, but there was no difference between groups infected intravenously. On day,1 of infection, neutropenic mice had significantly smaller fungal burdens than control mice. On day,7, neutropenic mice had significantly higher lung concentrations of IL-10, TNF-,, IL-4, and IL-12 than control mice, but there was no difference in IFN-, and MCP-1 levels. Neutrophils influenced the outcome of cryptococcal infection in mice through mechanisms that did not involve a reduction in early fungal burden. The absence of neutrophils in lung tissue during the initial stages of infection appeared to alter the inflammatory response in a manner thatwas subsequently beneficial to the host. Higher levels of Th1- and Th2-associated cytokines in neutropenic mice could have simultaneously promoted a strong cellular response while reducing inflammatory damage to the lung. Our results support the emerging concept that neutrophils play an important function in modulating the development of the immune response. [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]

Interleukin-13 directly promotes oesophagus production of CCL11 and CCL24 and the migration of eosinophils

CLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2010
C. V. Neilsen
Summary Background Eosinophilic oesophagitis (EE) is a clinico-pathologically defined oesophageal disorder that is characterized by eosinophil migration into oesophageal tissues. There is growing support for EE being an allergic disease and for a contribution of T-helper type 2 (Th2)-associated cytokines in disease pathogenesis. The respiratory system has been shown to be critical in driving the development of EE in animal models. However, the mechanisms underlying the recruitment of eosinophils into the oesophagus remain unclear. Objective We sought to investigate the influence of Th2-associated cytokines on the production of eosinophil-specific chemokines from the oesophagus directly. Methods In order to eliminate the potential involvement of the lung, we utilized isolated oesophageal rings. These were treated in vitro with IL-4 or IL-13 and the expression and production of CCL11 and CCL24 were determined. Results Our data demonstrate that IL-13 is a potent and direct inducer of both CCL11 and CCL24 production from the oesophagus, as is IL-4 also. The expression of CCL11 precedes CCL24 by several hours but then diminishes over time, as well as at high concentrations of IL-13. We demonstrate that there is an up-regulation of the inhibitory IL-13 receptor, IL-13R,2 but that IL-13R,1 remains unaltered. Oesophagus rings isolated from STAT6,/, mice were unable to produce CCL11 or CCL24 upon IL-13 treatment. Lastly, we demonstrate that oesophageal production of CCL11 and CCL24 upon IL-13 stimulation is sufficient to promote eosinophil migration. Conclusions IL-13 is capable of directly stimulating oesophageal tissue to produce eosinophil-attracting chemokines and drive eosinophil migration. Cite this as: C. V. Neilsen and P. J. Bryce, Clinical & Experimental Allergy, 2010 (40) 427,434. [source]

Immunoreactivity profile of peripheral blood mononuclear cells from patients with ragweed-induced allergic rhinitis

CLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2007
J. Sun
Summary Background Seasonal rhinitis is manifested by a series of nasal symptoms in response to exposure to seasonal allergens including ragweed pollen. Understanding its immunological mechanisms may help to better manage the disease. Objective We sought to determine comprehensively ragweed-induced cytokine and chemokine production by peripheral blood mononuclear cells from normal individuals and patients with seasonal rhinitis sensitized to ragweed pollen, and to assess its regulation by exogenous IL-10. Methods Cells were cultured in the presence or absence of a purified ragweed pollen extract with or without exogenous IL-10. Cytokines and chemokines were measured in the supernatant. Gene expression was evaluated using real-time quantitative reverse transcription PCR. Results Ragweed stimulation significantly increased the production of the Th2-associated cytokines IL-5, IL-9 and IL-13, the chemokines CCL17 and CCL22 and the regulatory cytokine IL-10 in allergic patients, whereas transforming growth factor-, (TGF-,) production was increased only in normal individuals. No difference was detected between groups in the production of the Th1 cytokine IFN-, or the Th1-affiliated chemokines CXCL10 and CXCL11. Exogenous IL-10 significantly suppressed spontaneous and induced production of both Th1- and Th2-associated cytokines and chemokines. Conclusion Our work demonstrated that locally manifested allergic rhinitis is underlined by a systemic Th2 immune response specific to allergens. The molecular pathogenesis of allergic rhinitis may be linked to a compromised allergen-specific immune regulation, e.g., reduced spontaneous and allergen-induced TGF-, production in patients compared with healthy controls. Our data also show that IL-10 inhibits both the effector and directional mechanisms of allergen-specific immune response, further supporting its potential therapeutic benefit in preventing and treating allergic diseases. [source]