title: IFN-alpha inhibits IL-3 priming of human basophil cytokine secretion but not leukotriene C4 and histamine release.
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-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.
authors: The Johns Hopkins Asthma and Allergy Center, Department of Medicine, Division of Clinical Immunology, Johns Hopkins University, Baltimore, Md 21224, USA.
authors: Yi-Hsing
authors: YH
authors: Chen
authors: Anja P
authors: AP
authors: Bieneman
authors: Peter S
authors: PS
authors: Creticos
authors: Kristin L
authors: KL
authors: Chichester
authors: John T
authors: JT
authors: Schroeder
mesh_terms: D000328:Adult; D001491:Basophils / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism*; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology; D007370:Interferon Type I / Q000494:pharmacology; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D018793:Interleukin-13 / Q000096:biosynthesis; D007377:Interleukin-3 / Q000494:pharmacology*; D017997:Leukotriene C4 / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000235:genetics
chemical_list: D016207:Cytokines; D007370:Interferon Type I; D016898:Interferon-alpha; D018793:Interleukin-13; D007377:Interleukin-3; D012333:RNA, Messenger; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta; D017997:Leukotriene C4; D007073:Immunoglobulin E; D006632:Histamine; D007371:Interferon-gamma