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


METHODS
12 weight-ranked Holstein calves.


METHODS
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.


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


CONCLUSIONS
By inducing neutrophil apoptosis, tilmicosin prevents further amplification of inflammatory injury in P haemolytica-infected lungs.
Chin
A C
AC
Department of Biological Sciences, University of Calgary, Alta., Canada.
Morck
D W
DW
Merrill
J K
JK
Ceri
H
H
Olson
M E
ME
Read
R R
RR
Dick
P
P
Buret
A G
AG
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal; D017209:Apoptosis; D001831:Body Temperature; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000382:microbiology; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy* / Q000276:immunology; D007975:Leukotriene B4 / Q000032:analysis; D008171:Lung Diseases / Q000188:drug therapy / Q000276:immunology / Q000662:veterinary*; D018942:Macrolides; D016978:Mannheimia haemolytica / Q000302:isolation & purification; D009504:Neutrophils / Q000276:immunology; D010326:Pasteurella Infections / Q000188:drug therapy / Q000276:immunology / Q000662:veterinary*; D010587:Phagocytosis; D015645:Tylosin / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018942:Macrolides; D007975:Leukotriene B4; C052319:tilmicosin; D015645:Tylosin