Cimetidine induces interleukin-18 production through H2-agonist activity in monocytes

Hideo Kohka Takahashi, Takeshi Watanabe, Akira Yokoyama, Hiromi Iwagaki, Tadashi Yoshino, Noriaki Tanaka, Masahiro Nishibori

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The present study demonstrates a possible mechanism for the improvement of gastrointestinal cancer patients' prognosis by the histamine receptor type 2 (H2R) antagonist cimetidine. This agent, but not the H2R antagonists ranitidine and famotidine, induced the production of an antitumor cytokine, interleukin (IL)-18, by human monocytes and dendritic cells (DC). In fact, ranitidine and famotidine antagonized cimetidine-induced IL-18 production. Cimetidine induced the activation of caspase-1, which is reported to modify immature IL-18 to mature/active IL-18, and the elevation of intracellular cAMP, leading to the activation of protein kinase A (PKA). The PKA inhibitor H89 abolished the IL-18 production induced by cimetidine. Moreover, the effects of cimetidine on IL-18 production were reproduced in peripheral blood mononuclear cells from wild-type mice, but not in those from H2R knockout mice. In conclusion, cimetidine, a partial agonist for H2R, has a pharmacological profile different from ranitidine and famotidine, possibly contributing to its antitumor activity on gastrointestinal cancers.

Original languageEnglish
Pages (from-to)450-453
Number of pages4
JournalMolecular pharmacology
Volume70
Issue number2
DOIs
Publication statusPublished - 2006

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of 'Cimetidine induces interleukin-18 production through H2-agonist activity in monocytes'. Together they form a unique fingerprint.

  • Cite this