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

Tumor necrosis factor-alpha (TNF) is an important mediator of endotoxi n-induced pathologic changes. To help define the role of TNF in equids with endotoxemia, the effects of pretreatment with a murine monoclona l antibody (MAB) against equine TNF were evaluated in Miniature Horses given endotoxin. Five horses were given TNF MAB at a dosage of 1.86 m g/kg of body weight, IV, and 5 were given control MAB. Five minutes la ter, lipopolysaccharide (LPS; Escherichia coli O55:B5), 0.25 mu g/kg, was given to all horses by bolus Iv infusion. Clinical signs of diseas e were monitored at intervals up to 24 hours after LPS infusion, and b lood was taken for determination of WBC count, PCV, plasma total prote in concentration, plasma TNF activity, and serum MAB concentration. Re duction of plasma TNF activity in anti-TNF-treated horses was highly s ignificant (P < 0.001), compared with that in control horses. Horses g iven TNF MAB had significantly improved clinical abnormality score (P < 0.010), lower heart rate (P < 0.001), and higher WBC count (P < 0.00 1), compared with horses given control MAB. Rectal temperature, respir atory rate, PCV, and plasma total protein concentration were not signi ficantly different between groups. Serum MAB concentration peaked at 6 8 mu g/ml 30 minutes after the end of antibody infusion in both groups . Neutralization of LPS-induced TNF activity reduced the hematologic a nd clinical responses of horses given LPS IV.