EFFECTS OF TUMOR-NECROSIS-FACTOR BLOCKADE ON INTERLEUKIN-6, LACTATE, THROMBOXANE, AND PROSTACYCLIN RESPONSES IN MINIATURE HORSES GIVEN ENDOTOXIN

A monoclonal antibody (MAB) against equine tumor necrosis factor-alpha (Eq TNF) was used to investigate the role of TNF in cytokine, eicosan oid, and metabolic responses of Miniature Horses given endotoxin. Plas ma concentrations of interleukin 6 (IL-6), lactate, thromboxane A(2) m etabolite, and prostacyclin metabolite (6-keto-PGF(1 alpha) were measu red in 10 Miniature Horses given 0.25 mu g 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 w ere 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 multip le intervals for 24 hours after LPS was given. Interleukin 6 bioactivi ty in plasma was measured, using IL-6-dependent cell line (B9). Eicosa noid activities were assessed by enzyme immunoassay, and plasma lactat e concentration was determined enzymatically. Data were analyzed by AN OVA and Tukey's honest significant difference test for significant (P < 0.05) effect of treatment, Horses given Eq TNF MAB had significantly (P < 0.050) lower peak mean +/- SEM IL-6 (59 +/- 29 U/ml), lactate (1 6 +/- 2.00 mg/dl), and 6-keto-PGF(1 alpha), (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(1 alpha). There was no effect of anti-TNF treatment on LPS-induced thromboxane A (2) metabolite production. Tumor necrosis factor mediated IL-6, lactat e, and prostacyclin responses, without affecting thromboxane productio n in horses given LTS.