Tilmicosin reduces lipopolysaccharide-stimulated bovine alveolar macrophage prostaglandin E(2) production via a mechanism involving phospholipases.

Abstract

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 E(2) (PGE(2)) production induced by Escherichia coli (O55:B5) lipopolysaccharide (LPS). Twenty-two healthy Holstein bull calves were used to study the effects of LPS-induced PGE(2) 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 hours apart, to four calves; four control calves received no treatment. Twenty-four hours 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 A(2) activity was examined in untreated calves. Treatment of calves with tilmicosin resulted in reduced LPS-induced alveolar macrophage PGE(2) production. Similar reductions in PGE(2) 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 A(2) activity induced by LPS was significantly reduced by prior tilmicosin treatment in vitro. Tilmicosin (in vivo and in vitro) appears to reduce the PGE(2) eicosanoid response of LPS-stimulated alveolar macrophages by reducing the in vitro substrate availability without altering in vitro COX-2 mRNA expression.

• Authors: Jeffrey Lakritz, Jeff W Tyler, Antoinette E Marsh, Mary Romesburg-Cockrell, Kathy Smith, Julie M Holle
• Journal: Veterinary therapeutics : research in applied veterinary medicine (Vet Ther) Vol. 3 Issue 1 Pg. 7-21 ( 2002) ISSN: 1528-3593 [Print] United States
• PMID: 12050824 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Actins
• Anti-Bacterial Agents
• DNA Primers
• Isoenzymes
• Lipopolysaccharides
• Macrolides
• RNA, Messenger
• Cyclooxygenase 2
• Prostaglandin-Endoperoxide Synthases
• Dinoprostone
• tilmicosin
• Tylosin

Topics

• Actins (genetics)
• Animals
• Anti-Bacterial Agents (administration & dosage, pharmacology, therapeutic use)
• Cattle
• Cell Line (drug effects)
• Cyclooxygenase 2
• DNA Primers
• Dinoprostone (biosynthesis)
• Injections, Subcutaneous (veterinary)
• Isoenzymes (genetics)
• Lipopolysaccharides (pharmacology)
• Macrolides
• Macrophages, Alveolar (drug effects, metabolism)
• Male
• Pasteurellosis, Pneumonic (drug therapy)
• Polymerase Chain Reaction (veterinary)
• Prostaglandin-Endoperoxide Synthases (genetics)
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction (veterinary)
• Tylosin (administration & dosage, analogs & derivatives, pharmacology, therapeutic use)