Histamine inhibits the production of interleukin-12 through interaction with H2 receptors.

IL-12 is essential for T helper 1 (Th1) development and in- hibits the induction of Th2 responses. Atopic diseases, which are characterized by Th2 responses, are associated with the overproduction of histamine. Here we present evidence that histamine, at physiological concentrations, strongly inhibits human IL-12 p40 and p70 mRNA and pro- tein production by human monocytes. The use of specific histamine receptor antagonists reveals that this inhibition is mediated via the H 2 receptor and induction of intracellular cAMP. The inhibition of IL-12 production is independent of IL-10 and IFN- g . The observation that histamine strongly reduces the production of the Th1-inducing cytokine IL-12 implies a positive feedback mechanism for the development of Th2 responses in atopic patients. ( J. Clin. Invest. 1998. 102:1866—1873.) Key words: cytokines ¥ allergy and immu- nology ¥ Th1 cells ¥ monocytes ¥ interferon gamma