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

J Allergy Clin Immunol. 2003 Nov;112(5):944-50. doi: 10.1016/j.jaci.2003.08.027.


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-alpha, 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-alpha 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-alpha on IL-3-mediated IL-13 secretion and basophil survival were also tested. IFN-alpha 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Basophils / drug effects
  • Basophils / metabolism*
  • Basophils / physiology
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cytokines / antagonists & inhibitors
  • Cytokines / metabolism*
  • Histamine / metabolism*
  • Humans
  • Immunoglobulin E / physiology
  • Interferon Type I / pharmacology
  • Interferon-alpha / pharmacology*
  • Interferon-gamma / pharmacology
  • Interleukin-13 / biosynthesis
  • Interleukin-3 / pharmacology*
  • Leukotriene C4 / metabolism
  • Middle Aged
  • RNA, Messenger / metabolism
  • Receptor, Interferon alpha-beta
  • Receptors, Interferon / genetics


  • Cytokines
  • Interferon Type I
  • Interferon-alpha
  • Interleukin-13
  • Interleukin-3
  • RNA, Messenger
  • Receptors, Interferon
  • Receptor, Interferon alpha-beta
  • Leukotriene C4
  • Immunoglobulin E
  • Histamine
  • Interferon-gamma