HISTAMINE AFFECTS INTERLEUKIN-4, INTERLEUKIN-5, AND INTERFERON-GAMMA PRODUCTION BY HUMAN T-CELL CLONES FROM THE AIRWAYS AND BLOOD

High levels of histamine can be found in the airways of asthma patient s. This study describes the effects of histamine on anti-CD3-induced p roduction of IL-4, IL-5, and IFN-gamma by T cell clones from subjects with allergic asthma and healthy subjects. T cell clones were obtained from bronchoalveolar lavage (BAL) fluid and blood. The number of clon es tested, and the percentage of clones in which histamine inhibited o r enhanced cytokine production by more than 25%, were as follows: IL-4 , 47, 8.5%, and 4.3%; IL-5, 43, 14%, and 30%; and IFN-gamma, 52, 40%, and 15%. Inhibition of IL-5 and IFN-gamma production was reversed by I L-2. The enhancement of IFN-gamma production was associated with an en hancement of both IL-2 production and proliferation. In 21% of the clo nes a combined effect consisting of inhibition of IFN-gamma production and enhancement of IL-5 production was found. This response was rever sed by H-2-receptor antagonists and was significantly associated with a histamine-induced increase in intracellular levels of cAMP. The role of cAMP in mediating the histamine effects was supported by the obser vations that the beta(2)-agonist salbutamol had effects similar to his tamine and that high concentrations of PGE(2) mimicked the inhibitory effects of histamine. Clones from BAL fluid and blood showed similar r esponses, as did clones from patients with asthma and from central sub jects. The enhancement of IFN-gamma production by histamine, however, was found only in clones from healthy subjects. The results warrant fu rther investigations on the role of cAMP in the regulation of cytokine production.