Tags

Type your tag names separated by a space and hit enter

Anti-inflammatory activity of macrolide antibiotics.
J Pharmacol Exp Ther. 2000 Jan; 292(1):156-63.JP

Abstract

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.

Authors+Show Affiliations

Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

10604943

Citation

Ianaro, A, et al. "Anti-inflammatory Activity of Macrolide Antibiotics." The Journal of Pharmacology and Experimental Therapeutics, vol. 292, no. 1, 2000, pp. 156-63.
Ianaro A, Ialenti A, Maffia P, et al. Anti-inflammatory activity of macrolide antibiotics. J Pharmacol Exp Ther. 2000;292(1):156-63.
Ianaro, A., Ialenti, A., Maffia, P., Sautebin, L., Rombolà, L., Carnuccio, R., Iuvone, T., D'Acquisto, F., & Di Rosa, M. (2000). Anti-inflammatory activity of macrolide antibiotics. The Journal of Pharmacology and Experimental Therapeutics, 292(1), 156-63.
Ianaro A, et al. Anti-inflammatory Activity of Macrolide Antibiotics. J Pharmacol Exp Ther. 2000;292(1):156-63. PubMed PMID: 10604943.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-inflammatory activity of macrolide antibiotics. AU - Ianaro,A, AU - Ialenti,A, AU - Maffia,P, AU - Sautebin,L, AU - Rombolà,L, AU - Carnuccio,R, AU - Iuvone,T, AU - D'Acquisto,F, AU - Di Rosa,M, PY - 1999/12/22/pubmed PY - 1999/12/22/medline PY - 1999/12/22/entrez SP - 156 EP - 63 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 292 IS - 1 N2 - 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/10604943/Anti_inflammatory_activity_of_macrolide_antibiotics_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10604943 DB - PRIME DP - Unbound Medicine ER -