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

Yi Hsing Chen, Anja P. Bieneman, Peter Socrates Creticos, Kristin L. Chichester, John Thomas Schroeder

Research output: Contribution to journalArticle

Abstract

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 TH1-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-α, a major type I IFN, affects the production of these TH2 cytokines and/or mediator release from these cells. Methods: Basophils isolated from blood were treated with IFN-α in the presence and absence of IL-3 priming before stimulating through the IgE receptor to release histamine, leukotriene C4, and IL-4. Effects of IFN-α on IL-3-mediated IL-13 secretion and basophil survival were also tested. IFN-α receptor expression was determined by RT-PCR. Results: IFN-α 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-α. This effect was specific for cytokine generation, because histamine and leukotriene C4 were unaffected. Furthermore, IFN-α blocked IL-13 secretion directly induced by IL-3. Although IFN-β also possessed some inhibitory activity, IFN-γ (a type II IFN) had no effect on basophil cytokine secretion. Basophils constitutively expressed mRNA for the type I IFN receptor, and IFN-α 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-α production negatively regulate allergic responses by also inhibiting priming of basophil cytokine release.

Original languageEnglish (US)
Pages (from-to)944-950
Number of pages7
JournalThe Journal of Allergy and Clinical Immunology
Volume112
Issue number5
DOIs
Publication statusPublished - Nov 2003

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Keywords

  • Cytokine priming
  • Histamine
  • Hypersensitivity
  • IgE
  • Innate immunity
  • Leukotriene

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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