IFN-α inhibits IL-3 priming of human basophil cytokine secretion but not leukotriene C4 and histamine release

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:112

Article

Chen, YH ; Bieneman, AP ; Creticos, PS ; Chichester, KL ; Schroeder, JT

关键词: IgE;    innate immunity;    hypersensitivity;    cytokine priming;    histamine;    leukotriene;   

DOI  :  10.1016/j.jaci.2003.08.027

来源: Elsevier

【 摘 要 】

Background: Innate immune responses play a critical role in determining the course of acquired immunity, including that associated with allergic disease. Type I interferons, which are generated early in these reactions, are important soluble factors that prime for T(H)1-like activity. Objective: Because human basophils secrete IL-4 and IL-13 in response to both IgE-dependent and IgE-independent stimuli, we tested whether IFN-alpha, a major type I IFN, affects the production of these T(H)2 cytokines and/or mediator release from these cells. Methods: Basophils isolated from blood were treated with IFN-alpha in the presence and absence of IL-3 priming before stimulating through the IgE receptor to release histamine, leukotriene C-4, and IL-4. Effects of IFN-alpha on IL-3-mediated IL-13 secretion and basophil survival were also tested. IFN-a receptor expression was determined by RT-PCR. Results: IFN-alpha specifically inhibited the effects IL-3 has on basophil cytokine secretion. Enhanced secretion of IL-4 resulting from IL-3 priming was significantly inhibited in cells concurrently cultured with IFN-alpha. This effect was specific for cytokine generation, because histamine and leukotriene C4 were unaffected. Furthermore, IFN-alpha blocked IL-13 secretion directly induced by IL-3. Although IFN-beta also possessed some inhibitory activity, IFN-gamma (a type II IFN) had no effect on basophil cytokine secretion. Basophils constitutively expressed mRNA for the type I IFN receptor, and IFN-alpha did not affect basophil viability with regard to inhibition of cytokine secretion. Conclusions: These results support the belief that early innate immune responses resulting in IFN-alpha production negatively regulate allergic responses by also inhibiting priming of basophil cytokine release.

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