Different modulation by histamine of IL-4 and interferon-gamma (IFN-gamma) release according to the phenotype of human Th0, Th1 and Th2 clones

Clin Exp Immunol. 1997 Jun;108(3):545-51. doi: 10.1046/j.1365-2249.1997.3791276.x.


Histamine, an important inflammatory mediator in allergic diseases and asthma, has been reported to have modulator effects on T cells, suggesting that the bronchial microenvironment may regulate the function of resident T cells. We examined the effect of histamine on the release of the Th2-associated cytokines IL-4 and IL-5 and the Th1-associated cytokine IFN-gamma by 30 CD4+ T cell clones from peripheral blood or bronchial biopsy of one atopic subject. Based on the IL-4/IFN-gamma ratio, the clones were ascribed to the Th2 (ratio > 1), Th0 (ratio > or = 0.1 and < or = 1) or Th1 (ratio < 0.1) phenotype. Histamine inhibited IFN-gamma production by Th1-like cells (P < 0.02, Kruskall-Wallis), especially from bronchial biopsy, but had no effect on IL-4 release. Regarding Th0 clones, histamine inhibited IL-4 production (P < 0.02) in a dose-dependent manner and slightly inhibited IFN-gamma production, but had no effect on Th2-like cells. Histamine had a heterogeneous and insignificant effect on IL-5 production. The H2-receptor antagonist ranitidine completely reversed the inhibition of IL-4 and IFN-gamma production, whereas the agonist dimaprit mimicked this effect. In contrast, H1- and H3-receptor agonists and antagonists had no significant effect. These data demonstrate that histamine has different effects on IL-4 and IFN-gamma release by T helper cells according to their phenotype via H2-receptors. This study extends the immunomodulatory effects of histamine which may contribute to the perpetuation of airway inflammation in asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clone Cells
  • Dinoprostone / pharmacology
  • Histamine / pharmacology*
  • Humans
  • Interferon-gamma / biosynthesis*
  • Interleukin-4 / biosynthesis*
  • Receptors, Histamine / drug effects
  • Th1 Cells / drug effects*
  • Th1 Cells / metabolism
  • Th2 Cells / drug effects*
  • Th2 Cells / metabolism


  • Receptors, Histamine
  • Interleukin-4
  • Histamine
  • Interferon-gamma
  • Dinoprostone