HISTAMINE INHIBITS THE PRODUCTION OF INTERLEUKIN-12 THROUGH INTERACTION WITH H-2 RECEPTORS

IL-12 is essential for T helper 1 (Th1) development and inhibits the i nduction of Th2 responses. Atopic diseases, which are characterized by Th2 responses, are associated with the overproduction of histamine. H ere we present evidence that histamine, at physiological concentration s, strongly inhibits human IL-12 p40 and p70 mRNA and protein producti on by human monocytes. The use of specific histamine receptor antagoni sts 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-gamma. The observation that histamine st rongly reduces the production of the Th1-inducing cytokine IL-12 impli es a positive feedback mechanism for the development of Th2 responses in atopic patients.