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Am. J. Respir. Cell Mol. Biol., Volume 18, Number 5, May, 1998 721-730

Histamine Affects Interleukin-4, Interleukin-5, and Interferon-gamma Production by Human T Cell Clones from the Airways and Blood

Frans H. Krouwels, Bernard E. A. Hol, René Lutter, Ben Bruinier, Aalt Bast, Henk M. Jansen, and Theo A. Out

Department of Pulmonology, Clinical and Laboratory Immunology Unit, Academic Medical Center, University of Amsterdam; Department of Pharmacochemistry, Free University; and Laboratory for Experimental and Clinical Immunology, Amsterdam, The Netherlands

High levels of histamine can be found in the airways of asthma patients. This study describes the effects of histamine on anti-CD3-induced production 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 clones tested, and the percentage of clones in which histamine inhibited or 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 IL-2. The enhancement of IFN-gamma production was associated with an enhancement of both IL-2 production and proliferation. In 21% of the clones a combined effect consisting of inhibition of IFN-gamma production and enhancement of IL-5 production was found. This response was reversed by H2-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 observations that the beta 2-agonist salbutamol had effects similar to histamine and that high concentrations of PGE2 mimicked the inhibitory effects of histamine. Clones from BAL fluid and blood showed similar responses, as did clones from patients with asthma and from control subjects. The enhancement of IFN-gamma production by histamine, however, was found only in clones from healthy subjects. The results warrant further investigations on the role of cAMP in the regulation of cytokine production.




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J. Sirois, G. Menard, A. S. Moses, and E. Y. Bissonnette
Importance of Histamine in the Cytokine Network in the Lung Through H2 and H3 Receptors: Stimulation of IL-10 Production
J. Immunol., March 15, 2000; 164(6): 2964 - 2970.
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Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 1998 American Thoracic Society. 		  CCM abstracts