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.
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.
Authors: Carrie D Fischer; Jennifer K Beatty; Stephanie C Duquette; Douglas W Morck; Merlyn J Lucas; André G Buret Journal: Antimicrob Agents Chemother Date: 2013-01-07 Impact factor: 5.191
Authors: A C Chin; W D Lee; K A Murrin; D W Morck; J K Merrill; P Dick; A G Buret Journal: Antimicrob Agents Chemother Date: 2000-09 Impact factor: 5.191
Authors: Carrie D Fischer; Jennifer K Beatty; Cheryl G Zvaigzne; Douglas W Morck; Merlyn J Lucas; A G Buret Journal: Antimicrob Agents Chemother Date: 2010-10-18 Impact factor: 5.191
Authors: Carrie D Fischer; Stephanie C Duquette; Bernard S Renaux; Troy D Feener; Douglas W Morck; Morley D Hollenberg; Merlyn J Lucas; Andre G Buret Journal: Antimicrob Agents Chemother Date: 2014-05-12 Impact factor: 5.191
Authors: D Desmonts de Lamache; R Moges; A Siddiq; T Allain; T D Feener; G P Muench; N McKenna; R M Yates; A G Buret Journal: PLoS One Date: 2019-08-23 Impact factor: 3.240