Anti-inflammatory benefits of tilmicosin in calves with Pasteurella haemolytica-infected lungs.

OBJECTIVES

To determine whether tilmicosin alters neutrophil infiltration or function, induces neutrophil apoptosis, and affects accumulation of leukotriene B4 (LTB4) or tumor necrosis factor-alpha (TNF-alpha) in lungs of calves experimentally infected with Pasteurella haemolytica.

ANIMALS

12 weight-ranked Holstein calves.

PROCEDURE

Calves were given 25% propylene glycol vehicle (n = 5) or tilmicosin (10 mg/kg of body weight; n = 6) subcutaneously, 18 hours and 15 minutes before intratracheal infection with 2 x 10(8) P haemolytica organisms. Two unmanipulated calves served as controls in some experiments. Rectal temperatures were recorded 15 minutes before, and at 3-hour intervals after infection for 24 hours. Samples obtained from bronchoalveolar lavage performed 3 and 24 hours after infection were used to assess colonization by P haemolytica, and neutrophil infiltration. Neutrophil phagocytosis of P haemolytica, membrane leakage as determined by trypan blue exclusion, oxidative function as determined by nitro blue tetrazolium reduction, and apoptosis, using electron microscopy and DNA fragmentation ELISA, were determined. SOluble TNF-alpha and LTB4 were measured from supernatants from bronchoalveolar lavage samples, using ELISA.

RESULTS

Treatment with tilmicosin resulted in significant (P < 0.05) clearance of P haemolytica and neutrophil apoptosis at 3 hours, and decreased concentration of LTB4 at 24 hours. Rectal temperatures, neutrophil infiltration, phagocytosis, oxidative functions, membrane leakage, and soluble TNF-alpha concentrations were not significantly affected by tilmicosin.

CONCLUSION

Tilmicosin effectively controlled P haemolytica infection, induced neutrophil apoptosis, reduced pulmonary inflammation, and did not affect neutrophil infiltration or function.

CLINICAL RELEVANCE

By inducing neutrophil apoptosis, tilmicosin prevents further amplification of inflammatory injury in P haemolytica-infected lungs.