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

Article Details

Citation

Takahashi HK, Watanabe T, Yokoyama A, Iwagaki H, Yoshino T, Tanaka N, Nishibori M

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

Mol Pharmacol. 2006 Aug;70(2):450-3. Epub 2006 May 24.

PubMed ID
16723495 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
CimetidineHistamine H2 receptorProteinHumans
Yes
Antagonist
Details
Pharmaco-proteomics
DrugDrug GroupsGeneGene IDChangeInteractionChromosome
CimetidineApproved InvestigationalIL183606
increased
Cimetidine results in increased expression of IL18 protein11q23.1
HistamineApproved InvestigationalIL183606
increased
Histamine results in increased expression of IL18 protein11q23.1