Anti-inflammatory activity of macrolide antibiotics

Ianaro, A., Ialenti, A., Maffia, P. , Sautebin, L., Rombolà, L., Carnuccio, R., Iuvone, T., D'Acquisto, F. and Di Rosa, M. (2000) Anti-inflammatory activity of macrolide antibiotics. Journal of Pharmacology and Experimental Therapeutics, 292(1), pp. 156-163. (PMID:10604943)

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The effect of four macrolide antibiotics (roxithromycin, clarithromycin, erythromycin, and azithromycin) on the generation of some mediators and cytokines involved in the inflammatory process has been studied both in vivo and in vitro. Rat carrageenin pleurisy was used as a model of acute inflammation, and the macrolides were administered (10, 20, and 40 mg/kg p.o.) 1 h before the carrageenin challenge. Exudate volume and leukocyte accumulation were both dose-dependently reduced by roxithromycin, clarithromycin and erythromycin in either normal or adrenalectomized animals. Furthermore, in normal rats, prostaglandin (PG)E(2), nitrate plus nitrite, and tumor necrosis factor-alpha levels in pleural exudate were significantly reduced by these macrolides. Roxithromycin appeared more effective than erythromycin and clarithromycin, whereas azithromycin only slightly affected the inflammatory reaction. None of the macrolides were able to modify leukotriene B(4) exudate levels. In vitro experiments have shown that the four macrolides (5-80 microM) reduced in a concentration-dependent manner the production of 6-keto-PGF(1alpha), NO(2)(-), tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 by lipopolysaccharide-stimulated J774 macrophages. In J774 cells, the inhibition of 6-keto-PGF(1alpha) and NO(2)(-) production by roxithromycin and erythromycin was not dependent on direct inhibition of cyclooxygenase-2 and inducible nitric oxide synthase activity because it appears to be related to the inhibition of cyclooxygenase-2 and inducible nitric oxide synthase protein expression. In conclusion, the present study shows that macrolide antibiotics have anti-inflammatory activity, which likely depends on their ability to prevent the production of proinflammatory mediators and cytokines, and suggest that these agents, particularly roxithromycin, can exert therapeutic effects independently of their antibacterial activity.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Maffia, Professor Pasquale
Authors: Ianaro, A., Ialenti, A., Maffia, P., Sautebin, L., Rombolà, L., Carnuccio, R., Iuvone, T., D'Acquisto, F., and Di Rosa, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Pharmacology and Experimental Therapeutics
Publisher:American Society for Pharmacology and Experimental Therapeutics
ISSN (Online):1521-0103

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