AAC Accepts, published online ahead of print on 1 October 2007

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Antimicrob. Agents Chemother. doi:10.1128/AAC.00985-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Rifampin inhibits PGE₂ production and arachidonic acid release in human alveolar epithelial cells

Yael Yuhas^*, Inbar Azoulay-Alfaguter, Eva Berent, and Shai Ashkenazi

Laboratory of Infectious Diseases, Felsenstein Medical Research Center and Department of Pediatrics A, Schneider Children's Medical Center of Israel, Petach Tikva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

^* To whom correspondence should be addressed. Email: yuhas{at}post.tau.ac.il.

Rifampin, a potent antimicrobial agent, is a major drug in the treatment of tuberculosis. There is evidence that rifampin also serves as an immunomodulator. Based on findings that arachidonic acid and its metabolites are involved in the pathogenesis of Mycobacterium tuberculosis infections, we investigated whether rifampin affects prostaglandin E₂ (PGE₂) production in human alveolar epithelial cells stimulated with interleukin-1. Rifampin caused a dose–dependent inhibition of PGE₂ production. At doses of 100, 50, and 25 µg/ml it inhibited PGE₂ production by 75%, 59% and 45%, respectively (p<0.001). Regarding the mechanism involved, rifampin caused a time- and dose-dependent inhibition of arachidonic acid release from the alveolar cells. At doses of 100, 50, 25 and 10 µg/ml it significantly inhibited the release of arachidonic acid by 93%, 64%, 58%, and 35%, respectively (p<0.001). Rifampin did not affect the phosphorylation of cytosolic phospholipase A₂ or the expression of cyclooxygenase2. The inhibition of PGE₂, and presumably other arachidonic acid products, probably contributes to the efficacy of rifampin in the treatment of tuberculosis, and may explain some of its adverse effects.

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