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

Jana L. Cargile From the Departments of Large Animal Clinical Sciences (Cargile, MacKay, Skelley) and Comparative and Experimental Pathology (Dankert), College of Veterinary Medicine, University of Florida, PO Box 100136, Gainesville, FL 32610-0136.

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Robert J. MacKay From the Departments of Large Animal Clinical Sciences (Cargile, MacKay, Skelley) and Comparative and Experimental Pathology (Dankert), College of Veterinary Medicine, University of Florida, PO Box 100136, Gainesville, FL 32610-0136.

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John R. Dankert From the Departments of Large Animal Clinical Sciences (Cargile, MacKay, Skelley) and Comparative and Experimental Pathology (Dankert), College of Veterinary Medicine, University of Florida, PO Box 100136, Gainesville, FL 32610-0136.

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Leslie Skelley From the Departments of Large Animal Clinical Sciences (Cargile, MacKay, Skelley) and Comparative and Experimental Pathology (Dankert), College of Veterinary Medicine, University of Florida, PO Box 100136, Gainesville, FL 32610-0136.

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SUMMARY

Tumor necrosis factor-α (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 µg/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 hematologic and clinical responses of horses given 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 µg/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.

SUMMARY

Tumor necrosis factor-α (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 µg/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 hematologic and clinical responses of horses given 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 µg/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.

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