Tilmicosin reduces lipopolysaccharide-stimulated bovine alveolar macrophage prostaglandin E (2) production via a mechanism involving phospholipases
Lakritz, J.; Tyler, J.W.; Marsh, A.E.; Romesburg-Cockrell, M.; Smith, K.; Holle, J.M.
Veterinary Therapeutics Research in Applied Veterinary Medicine 3(1): 7-21
2002
ISSN/ISBN: 1528-3593 PMID: 12050824 Document Number: 546053
Tilmicosin is a potent antimicrobial with broad-spectrum activity against the bacterial agents involved in the bovine respiratory disease complex. Recent studies indicate that in addition to being bactericidal, tilmicosin is capable of modulating inflammation in the lung. A series of experiments were designed to determine whether tilmicosin alters alveolar macrophage-prostaglandin E2 (PGE2) production induced by Escherichia coli (O55:B5) lipopolysaccharide (LPS). 22 healthy Holstein bull calves were used to study the effects of LPS-induced PGE2 production of alveolar macrophages after in vivo or in vitro treatment with tilmicosin. In experiment 1, tilmicosin was given by subcutaneous injection (15 mg/kg) twice, 48 h apart, to four calves; four control calves received no treatment. 24 h after the second treatment, alveolar macrophages were stimulated with LPS in vitro. In experiment 2, alveolar macrophages from five untreated calves were harvested and treated in vitro with tilmicosin, followed by LPS stimulation. In experiment 3, the ability of in vitro tilmicosin treatment to alter the expression of LPS-induced cyclooxygenase-2 (COX-2) mRNA was evaluated. In experiments 4 and 5, secretory phospholipase A2 activity was examined in untreated calves. Treatment of calves with tilmicosin resulted in reduced LPS-induced alveolar macrophage PGE2 production. Similar reductions in PGE2 by LPS-stimulated alveolar macrophages after in vitro tilmicosin treatment were noted. This in vitro tilmicosin treatment was not associated with reduction of the expression of LPS-induced COX-2. Alveolar macrophage phospholipase A2 activity induced by LPS was significantly reduced by prior tilmicosin treatment in vitro. Tilmicosin (in vivo and in vitro) appears to reduce the PGE2 eicosanoid response of LPS-stimulated alveolar macrophages by reducing the in vitro substrate availability without altering in vitro COX-2 mRNA expression.