Histamine inhibits the production of interleukin-12 through interaction with H2 receptors.
IL-12 is essential for T helper 1 (Th1) development and inhibits 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 protein production by human monocytes. The use of specific histamine receptor antagonists reveals that this inhibition is mediated via the H2 receptor and induction of intracellular cAMP. The inhibition of IL-12 production is independent of IL-10 and IFN-gamma. 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.
van der Pouw Kraan
T C
TC
CLB, Sanquin Blood Supply Foundation, Department of Auto-Immune Diseases, Laboratory for Experimental and Clinical Immunology, Academic Medical Centre, University of Amsterdam, 1066CX Amsterdam, The Netherlands. TpouwK@CLB.nl
Snijders
A
A
Boeije
L C
LC
de Groot
E R
ER
Alewijnse
A E
AE
Leurs
R
R
Aarden
L A
LA
D015232:Dinoprostone / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D018664:Interleukin-12 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D011899:Ranitidine / Q000494:pharmacology; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014311:Triprolidine / Q000494:pharmacology
D017442:Histamine Agonists; D006633:Histamine Antagonists; D006635:Histamine H2 Antagonists; D007093:Imidazoles; D007378:Interleukins; D012333:RNA, Messenger; D011970:Receptors, Histamine H2; D018664:Interleukin-12; D014311:Triprolidine; D006632:Histamine; D011899:Ranitidine; D013890:Thiourea; D015232:Dinoprostone; C086108:clobenpropit