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Mediators of Inflammation
Volume 8, Issue 4-5, Pages 199-204
http://dx.doi.org/10.1080/09629359990351

Suppressive Activity of a Macrolide Antibiotic, Roxithromycin, on Pro-Inflammatory Cytokine Production in Vitro and in Vivo

1Department of Otolaryngology, School of Medicine, Showa University, 1–5-8 Hatanodai, Shinagawa-ku, Tokyo 142–8555, Japan
2Department of Physiology, School of Medicine, Showa University, 1–5-8 Hatanodai, Shinagawa-ku, Tokyo 142–8555, Japan

Copyright © 1999 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

This study was designed to examine the influence of a macrolide antibiotic, roxithromycin (RXM), on the production of pro-inflammatory cytokines, interleukin (IL)-1β and tumor necrosis factor (TNF)-α. In the first experiments, we examined the effect of RXM on in vitro cytokine production from lipopolysaccharide (LPS)-stimulated human peripheral blood monocytes. The monocytes were cultured in the presence of various doses of the agent. After 24 h, the culture supernatants were obtained and assayed for IL-1β and TNF-α contents by enzyme-linked immunosorbent assay. RXM suppressed the in vitro production of IL-1β and TNF-α in response to LPS stimulation. This was dose dependent and first noted at a concentration of as little as 0.05 μg/ml, which is much lower than therapeutic blood levels. In the second part of the experiments, we examined the influence of RXM on the appearance of IL-1β and TNF-α in mouse lung extract induced by LPS inhalation. RXM was administered orally into BALB/c mice at a single dose of 2.5 mg/kg once a day for 5-12 weeks. These mice were then instilled with LPS into the trachea and examined for the presence of cytokines in aqueous lung extracts. Pretreatment of mice with RXM for 5 weeks did not influence of the appearance of both IL-1β and TNF-α in aqueous lung extracts. However, pretreatment for more than 7 weeks dramatically suppressed the cytokine appearance in the extracts.