RECOMBINANT BOVINE SOMATOTROPIN BLUNTS PLASMA TUMOR-NECROSIS-FACTOR-ALPHA, CORTISOL, AND THROMBOXANE-B-2 RESPONSES TO ENDOTOXIN IN-VIVO

In vivo studies determined the effects of recombinant bovine somatotropin (bST; sometribove) administration (0.1 mg/kg.day, im) to calves on the increases in plasma immunoreactive tumor necrosis factor-alpha (TNF alpha), prostacyclin [6-keto-prostaglandin F-1 alpha (6KP)I, thromboxane-B-2 (TXB), and cortisol (C) that occurred after endotoxin challenge (ET). Two ETs were administered 5 days apart to test the effect of bST on the natural attenuation of hormone and cytokine responses that occurs after repeated challenge with endotoxin. Calves (n = 6) were treated with bST for 5 days. On day 6, the first ET was administered (Escherichia coli; 055:B5; 0.2 mu g/kg, iv). Blood was sampled before and hourly after ET through 6 h. For the next 4 days, bST injections continued, and ET was repeated 1 day later. Six additional calves were treated with bicarbonate buffer as contemporary controls for the bST and were similarly challenged with endotoxin. Plasma TNF alpha, C, 6KP, and TXB were significantly increased after each ET. The increases in TNF alpha, C, and TXB were blunted after the second ET compared to those after the first in both untreated and bST-treated animals. The increases in plasma TNF alpha and C and peak plasma TXB and TXB/6KP ratios were smaller in bST-treated than in untreated after the first ET. TNF alpha receptor binding was studied in hepatic microsomal fractions from three bST-treated and three untreated calves. Microsomal fractions from bST-treated calves bound 40% less TNF alpha (5.97 us. 9.96 pmol/mg) than similar fractions from controls. The data indicate that bST decreases TNF alpha, TXB, and C responses to ET and reduces the TNF alpha-binding capacity of hepatic membranes, suggesting a multiplicity of sites where bST might affect the physiological response to endotoxin.