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  • Author or Editor: John R. Dankert x
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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.

Free access
in American Journal of Veterinary Research

SUMMARY

A monoclonal antibody (mab) against equine tumor necrosis factor-α (Eq tnf) was used to investigate the role of tnf in cytokine, eicosanoid, and metabolic responses of Miniature Horses given endotoxin. Plasma concentrations of interleukin 6 (il-6), lactate, thromboxane A2 metabolite, and prostacyclin metabolite (6-keto-pgf ) were measured in 10 Miniature Horses given 0.25 µg of lipopolysaccharide (lps; Escherichia coli O55:B5)/kg of body weight. Five horses were given Eq tnf mab and 5 were given isotype-matched mab as control. All horses were given 1.86 mg of antibody/kg by iv infusion, 5 minutes before lps was given iv. Blood samples were taken 20 minutes before and at multiple intervals for 24 hours after lps was given. Interleukin 6 bioactivity in plasma was measured, using il-6-dependent cell line (B9). Eicosanoid activities were assessed by enzyme immunoassay, and plasma lactate concentration was determined enzymatically. Data were analyzed by anova and Tuke's honest significant difference test for significant (P < 0.05) effect of treatment. Horses given Eq tn mab had significantly (P < 0.050) lower peak mean ± sem il-6 (59 ± 29 U/ml), lactate (16 ± 2.00 mg/dl), and 6-keto-pgf (254 ± 79 pg/ml) values then did horses given control mab (880 ± 375 U/ml for il-6; 26 ± 0.04 mg/dl for lactate; and 985 ± 290 pg/ml for 6-keto-pgf ). There was no effect of anti-tnf treatment on lps-induced thromboxane A2 metabolite production. Tumor necrosis factor mediated il-6, lactate, and prostacyclin responses, without affecting thromboxane production in horses given lps.

Free access
in American Journal of Veterinary Research