Effects of tumor necrosis factor blockade on interleukin 6, lactate, thromboxane, and prostacyclin responses in 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

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.

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.

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