Effects of tylosin, tilmicosin and tulathromycin on inflammatory mediators in bronchoalveolar lavage fluid of lipopolysaccharide-induced lung injury.

摘要

The aim of this study was to determine the anti-inflammatory effects of macrolides through kinetic parameters in bronchoalveolar lavage fluid (BALF) of lipopolysaccharide-induced lung injury. Rats were divided into four groups: lipopolysaccharide (LPS), LPS+tylosin, LPS+tilmicosin and LPS+tulathromycin. BALF samples were collected at sampling times. TNF, IL-1 beta , IL-6, IL-10 and 13,14-dihydro-15-keto-prostaglandin F₂ alpha (PGM) and C-reactive protein (CRP) were analysed. Area under the curve (AUC) and maximum plasma concentration (C_max) values of inflammatory mediators were determined by a pharmacokinetic computer programme. When inflammatory mediator concentrations were compared between the LPS group and other groups for each sampling time, the three macrolides had no pronounced depressor effect on cytokine levels, but they depressed PGM and CRP levels. In addition, tylosin and tilmicosin decreased the AUC_0-24 level of TNF, while tilmicosin decreased the AUC_0-24 level of IL-10. Tylosin and tulathromycin decreased the AUC_0-24 of PGM, and all three macrolides decreased the AUC_0-24 of CRP. Especially tylosin and tulathromycin may have more expressed anti-inflammatory effects than tilmicosin, via depressing the production of inflammatory mediators in the lung. The AUC may be used for determining the effects of drugs on inflammation. In this study, the antiinflammatory effects of these antibiotics were evaluated with kinetic parameters as a new and different approach.