Different modulation by histamine of IL-4 and interferon-gamma (IFN-gamma) release according to the phenotype of human Th0, Th1 and Th2 clones.
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.
Lagier
B
B
INSERM U454, Hôpital Arnaud de Villeneuve, Montpellier, France.
Lebel
B
B
Bousquet
J
J
Pène
J
J
D002999:Clone Cells; D015232:Dinoprostone / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D011968:Receptors, Histamine / Q000187:drug effects; D018417:Th1 Cells / Q000187:drug effects* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects* / Q000378:metabolism
D011968:Receptors, Histamine; D015847:Interleukin-4; D006632:Histamine; D007371:Interferon-gamma; D015232:Dinoprostone