Histamine enhances interleukin (IL)-1-induced IL-1 gene expression and protein synthesis via H2 receptors in peripheral blood mononuclear cells. Comparison with IL-1 receptor antagonist

J Clin Invest. 1993 Jul;92(1):281-7. doi: 10.1172/JCI116562.

Abstract

Histamine and IL-1 have been implicated in the pathogenesis of chronic inflammatory diseases, such as pulmonary allergic reactions and rheumatoid arthritis. We therefore investigated whether histamine modulated the synthesis of IL-1 beta. Human PBMC were stimulated with IL-1 alpha (10 ng/ml) in the absence or presence of histamine (10(-9)-10(-4) M). Histamine alone did not induce protein synthesis or mRNA accumulation for IL-1 beta. IL-1 alpha-induced IL-1 beta synthesis was enhanced two to threefold by histamine concentrations from 10(-6)-10(-4) M. Cimetidine, an H2 receptor antagonist, reversed the histamine (10(-5) M)-mediated increase in IL-1 alpha-induced IL-1 beta synthesis. Diphenhydramine, an H1 receptor antagonist, had no effect. Indomethacin, a cyclooxygenase inhibitor, significantly reduced IL-1 alpha-induced IL-1 beta synthesis, but had no effect on the histamine-mediated increase in IL-1 alpha-induced IL-1 beta synthesis. Histamine (10(-5) M) enhanced and sustained IL-1 beta mRNA levels in IL-1 alpha-stimulated PBMC. However, histamine reduced IL-1 beta mRNA half-life (2.4 vs 1.2 h), suggesting that histamine enhances IL-1 alpha-induced IL-1 beta synthesis at the level of transcriptional activation. On the other hand, histamine (10(-5) M) did not affect IL-1 alpha-induced synthesis of IL-1 receptor antagonist. These results suggest that mast cells may sustain chronic inflammatory processes by upregulating self-induction of IL-1 through histamine release.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Dinoprostone / pharmacology
  • Gene Expression / drug effects
  • Histamine / administration & dosage*
  • Humans
  • In Vitro Techniques
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / administration & dosage*
  • Interleukin-1 / genetics*
  • Leukocytes, Mononuclear / metabolism*
  • Lipopolysaccharides / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Histamine H2 / physiology*
  • Sialoglycoproteins / genetics*
  • Signal Transduction

Substances

  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Lipopolysaccharides
  • RNA, Messenger
  • Receptors, Histamine H2
  • Sialoglycoproteins
  • Histamine
  • Dinoprostone