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

A. C. Chin From the Departments of Biological Sciences (Chin, Morck, Ceri, Buret), Microbiology and Infectious Diseases (Olson, Read), and Biofilm Research Group (Morck, Ceri, Olson, Read, Buret), the University of Calgary, Alta, Canada T2N 1N4; and Provel Division Eli Lilly Canada Inc, Guelph, Ont, Canada N1G 4T2 (Merrill, Dick).

Search for other papers by A. C. Chin in
Current site
Google Scholar
PubMed
Close
 BSc
,
D. W. Morck From the Departments of Biological Sciences (Chin, Morck, Ceri, Buret), Microbiology and Infectious Diseases (Olson, Read), and Biofilm Research Group (Morck, Ceri, Olson, Read, Buret), the University of Calgary, Alta, Canada T2N 1N4; and Provel Division Eli Lilly Canada Inc, Guelph, Ont, Canada N1G 4T2 (Merrill, Dick).

Search for other papers by D. W. Morck in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
J. K. Merrill From the Departments of Biological Sciences (Chin, Morck, Ceri, Buret), Microbiology and Infectious Diseases (Olson, Read), and Biofilm Research Group (Morck, Ceri, Olson, Read, Buret), the University of Calgary, Alta, Canada T2N 1N4; and Provel Division Eli Lilly Canada Inc, Guelph, Ont, Canada N1G 4T2 (Merrill, Dick).

Search for other papers by J. K. Merrill in
Current site
Google Scholar
PubMed
Close
 PhD
,
H. Ceri From the Departments of Biological Sciences (Chin, Morck, Ceri, Buret), Microbiology and Infectious Diseases (Olson, Read), and Biofilm Research Group (Morck, Ceri, Olson, Read, Buret), the University of Calgary, Alta, Canada T2N 1N4; and Provel Division Eli Lilly Canada Inc, Guelph, Ont, Canada N1G 4T2 (Merrill, Dick).

Search for other papers by H. Ceri in
Current site
Google Scholar
PubMed
Close
 PhD
,
Μ. E. Olson From the Departments of Biological Sciences (Chin, Morck, Ceri, Buret), Microbiology and Infectious Diseases (Olson, Read), and Biofilm Research Group (Morck, Ceri, Olson, Read, Buret), the University of Calgary, Alta, Canada T2N 1N4; and Provel Division Eli Lilly Canada Inc, Guelph, Ont, Canada N1G 4T2 (Merrill, Dick).

Search for other papers by Μ. E. Olson in
Current site
Google Scholar
PubMed
Close
 MSc, DVM
,
R. R. Read From the Departments of Biological Sciences (Chin, Morck, Ceri, Buret), Microbiology and Infectious Diseases (Olson, Read), and Biofilm Research Group (Morck, Ceri, Olson, Read, Buret), the University of Calgary, Alta, Canada T2N 1N4; and Provel Division Eli Lilly Canada Inc, Guelph, Ont, Canada N1G 4T2 (Merrill, Dick).

Search for other papers by R. R. Read in
Current site
Google Scholar
PubMed
Close
 MD, PhD
,
P. Dick From the Departments of Biological Sciences (Chin, Morck, Ceri, Buret), Microbiology and Infectious Diseases (Olson, Read), and Biofilm Research Group (Morck, Ceri, Olson, Read, Buret), the University of Calgary, Alta, Canada T2N 1N4; and Provel Division Eli Lilly Canada Inc, Guelph, Ont, Canada N1G 4T2 (Merrill, Dick).

Search for other papers by P. Dick in
Current site
Google Scholar
PubMed
Close
 DVM, MSc
, and
A. G. Buret From the Departments of Biological Sciences (Chin, Morck, Ceri, Buret), Microbiology and Infectious Diseases (Olson, Read), and Biofilm Research Group (Morck, Ceri, Olson, Read, Buret), the University of Calgary, Alta, Canada T2N 1N4; and Provel Division Eli Lilly Canada Inc, Guelph, Ont, Canada N1G 4T2 (Merrill, Dick).

Search for other papers by A. G. Buret in
Current site
Google Scholar
PubMed
Close
 PhD

Click on author name to view affiliation information

Abstract

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-α) 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 × 108 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-α 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-α 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. (Am J Vet Res 1998;59:765-771)

Abstract

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-α) 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 × 108 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-α 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-α 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. (Am J Vet Res 1998;59:765-771)

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 115 115 13
PDF Downloads 41 41 2
Advertisement