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

Abstract

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 beta2-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.

Suplatast Tosilate Inhibits Histamine Signaling by Direct and Indirect Down-Regulation of Histamine H1 Receptor Gene Expression through Suppression of Histidine Decarboxylase and IL-4 Gene Transcriptions

“…Pretreatment with IL-4 primes the release of histamine, prostaglandins, leukotrienes, and cytokines in response to FcRI (21,22). Histamine, on the other hand, modulates the releases of IL-4 and IFN-␥ from T cells (23) and induces the release of IL-5 (24).…”

Importance of Histamine in the Cytokine Network in the Lung Through H2 and H3 Receptors: Stimulation of IL-10 Production

“…Furthermore, there is increasing evidence suggesting that histamine may be involved in the regulation of cytokine networks. Histamine can inhibit the release of IL-1, IL-2, IFN-␥, and TNF (11)(12)(13)(14)(15) and increase the release of IL-5 (13), , and IL-8 (17).…”

Repeated Pre-treatment With Antihistamines Causes Transcriptional Up-regulations of Histamine H1 Receptor and Interleukin-4 Genes in Toluene-2,4-diisocyanate–Sensitized Rats

“…IL-4, which regulates the production of IgE by B cells and the expression of leukotriene C4 synthase by mast cells, enhances the Th2 responses (16,17). Histamine is reported to modulate the releases of IL-4 and IFN-γ from T cells (18) and induce the releases of IL-5 (19) and 21). Thus, histaminecytokine networks are suggested to be important in allergic inflammation.…”