title: Effect of treatment with a monoclonal antibody against equine tumor necrosis factor (TNF) on clinical, hematologic, and circulating TNF responses of miniature horses given endotoxin.
abstract: Tumor necrosis factor-alpha (TNF) is an important mediator of endotoxin-induced pathologic changes. To help define the role of TNF in equids with endotoxemia, the effects of pretreatment with a murine monoclonal antibody (MAB) against equine TNF were evaluated in Miniature Horses given endotoxin. Five horses were given TNF MAB at a dosage of 1.86 mg/kg of body weight, IV, and 5 were given control MAB. Five minutes later, lipopolysaccharide (LPS; Escherichia coli O55:B5), 0.25 microgram/kg, was given to all horses by bolus IV infusion. Clinical signs of disease were monitored at intervals up to 24 hours after LPS infusion, and blood was taken for determination of WBC count, PCV, plasma total protein concentration, plasma TNF activity, and serum MAB concentration. Reduction of plasma TNF activity in anti-TNF-treated horses was highly significant (P < 0.001), compared with that in control horses. Horses given TNF MAB had significantly improved clinical abnormality score (P < 0.010), lower heart rate (P < 0.001), and higher WBC count (P < 0.001), compared with horses given control MAB. Rectal temperature, respiratory rate, PCV, and plasma total protein concentration were not significantly different between groups. Serum MAB concentration peaked at 68 micrograms/ml 30 minutes after the end of antibody infusion in both groups. Neutralization of LPS-induced TNF activity reduced the hematologic and clinical responses of horses given LPS IV.
authors.affiliation: Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32610-0136, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Cargile
authors.forename: R J
authors.initials: RJ
authors.lastname: MacKay
authors.forename: J R
authors.initials: JR
authors.lastname: Dankert
authors.forename: L
authors.initials: L
authors.lastname: Skelley
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001798:Blood Proteins / Q000187:drug effects / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects*; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006736:Horses; D007074:Immunoglobulin G / Q000097:blood; D007700:Kinetics; D007958:Leukocyte Count / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D012119:Respiration / Q000187:drug effects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D001798:Blood Proteins; D004731:Endotoxins; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha