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 somatotro pin (bST; sometribove) administration (0.1 mg/kg.day, im) to calves on the increases in plasma immunoreactive tumor necrosis factor-alpha (T NF alpha), prostacyclin [6-keto-prostaglandin F-1 alpha (6KP)I, thromb oxane-B-2 (TXB), and cortisol (C) that occurred after endotoxin challe nge (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 t reated with bST for 5 days. On day 6, the first ET was administered (E scherichia coli; 055:B5; 0.2 mu g/kg, iv). Blood was sampled before an d hourly after ET through 6 h. For the next 4 days, bST injections con tinued, and ET was repeated 1 day later. Six additional calves were tr eated with bicarbonate buffer as contemporary controls for the bST and were similarly challenged with endotoxin. Plasma TNF alpha, C, 6KP, a nd TXB were significantly increased after each ET. The increases in TN F alpha, C, and TXB were blunted after the second ET compared to those after the first in both untreated and bST-treated animals. The increa ses in plasma TNF alpha and C and peak plasma TXB and TXB/6KP ratios w ere smaller in bST-treated than in untreated after the first ET. TNF a lpha receptor binding was studied in hepatic microsomal fractions from three bST-treated and three untreated calves. Microsomal fractions fr om 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 decr eases TNF alpha, TXB, and C responses to ET and reduces the TNF alpha- binding capacity of hepatic membranes, suggesting a multiplicity of si tes where bST might affect the physiological response to endotoxin.