Inflammation, Phagocytosis and Effect of Flunixin Meglumine During Endotoxin-Induced Mastitis (Therapy, Prostaglandins)
Anderson, Kevin Lindsay
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Permalink
https://hdl.handle.net/2142/71315
Description
Title
Inflammation, Phagocytosis and Effect of Flunixin Meglumine During Endotoxin-Induced Mastitis (Therapy, Prostaglandins)
Author(s)
Anderson, Kevin Lindsay
Issue Date
1984
Department of Study
Veterinary Medical Science
Discipline
Veterinary Medical Science
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Veterinary Science
Abstract
The objectives were to determine the following in endotoxin-induced mastitis: (1) milk concentrations of thromboxane B(,2) (TXB(,2)) and prostaglandin F(,2(alpha)) (PGF(,2(alpha))); (2) the pharmacokinetics of flunixin meglumine in lactating cattle; (3) the clinical efficacy of the flunixin meglumine and its effect on milk and plasma TXB(,2) and PGF(,2(alpha)); and (4) changes of whey immunoglobulins and ability of wheys to enhance neutrophil phagocytosis of Staphylococcus aureus.
Initial studies were conducted on clinical cases of coliform mastitis and showed increased TXB(,2) and PGF(,2(alpha)) in quarter milk samples. In studies in 5 cows inoculated (in single quarters) with Escherichia coli, milk bovine serum albumin and somatic cell concentrations increased significantly in inoculated quarters. Concentrations of TXB(,2) and PGF(,2(alpha)) were not significantly elevated in inoculated quarters. In further studies, 10 (mu)g of endotoxin (E. coli 026:(beta)6 lipopolysaccharide) was inoculated in single quarters of 12 cows. Concentrations of TXB(,2) in milk were elevated in endotoxin-treated quarters. Concentrations of PGF(,2(alpha)) in milk were not significantly different among quarter treatments.
Concentrations of flunixin were determined in plasma and milk of 6 cows following administration of 1.1 mg/kg doses of flunixin meglumine in a two-way cross-over experiment. The pharmacokinetics of flunixin were best described by a two-compartment open model with a mean plasma half-life (t- 1/2 (beta)) of 3.6 hours. A dosing schedule of 1.1 mg/kg at 8-hour intervals was indicated.
Flunixin treatment IM (6 cows) was compared to saline IM (6 cows) in 12 cows administered 10 (mu)g of endotoxin in single quarters. Flunixin reduced rectal temperatures, depression scores, and quarter inflammation as well as 15-keto-13,14-dihydro PGF(,2(alpha)) in jugular vein plasma and TXB(,2) in milk. Milk indicators of acute mastitis and milk production were not significantly different between IM treatments.
Whey immunoglobulin concentrations and the ability of wheys to enhance phagocytosis of Staphylococcus aureus by neutrophils were determined in samples of 12 cows following inoculation of endotoxin. IgG(,1), IgG(,2) and IgM and ability of wheys to enhance phagocytosis increased in endotoxin-treated quarters. Immunoglobulins (primarily IgG(,2)), divalent cations and complement all contributed to the increased phagocytosis.
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