STUDY OF SEPTIC SHOCK IN THE NONHUMAN PRIMATE - RELATIONSHIP OF PATHOPHYSIOLOGICAL RESPONSE TO THERAPY WITH ANTI-TNF ANTIBODY

Therapy with anti-TNF antibody is reported to be effective in preventi ng morbidity and mortality in baboons given lethal infusions of Echeri chia coli. Treated animals survived, and organ histopathology was abse nt when antibody was administered early after lethal infusions of E. c oli. The present study explored the relationship between antibody dosa ge, pathophysiology, and survivability from shock. When antibody dose was decreased lungs, kidneys, adrenals, spleen, and fiver were injured as shown by increased vascular congestion, hemorrhage, edema, and nec rosis of tissues. Survival was also affected. All animals treated with 15 mg/kg antibody survived as reported earlier; less than 60% survive d with 7.5 mg/kg; 9% survived with 5.0 mg/kg, and all died with 1.5 mg /kg. Serum concentrations of interleukin-6 (IL-6) increased markedly a s dose of antibody decreased. The increases in concentrations of IL-6 were associated with increases in morbidity and mortality following E. Coli administration. (C) 1995 Wiiey-Liss, Inc.