TUMOR-NECROSIS-FACTOR ANTIBODY TREATMENT OF SEPTIC BABOONS REDUCES THE PRODUCTION OF SUSTAINED T-CELL SUPPRESSIVE FACTORS

Post-traumatic septic complications result from impaired cell-mediated immune function, which is caused in part by circulating T-cell suppre ssive factors (TSFs). We examined whether tumor necrosis factor alpha (TNF-alpha) antibody treatment in a baboon sepsis model influences the production of TSFs, including interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta). Sepsis was induced in anesthetized bab oons by Escherichia coil infusion, and caused an increase in plasma le vels of TNF, TSF activity, IL-10, and active TGF-beta, as well as a de crease in latent TGF-beta. TNF antibody pretreatment reduced TNF level s by 98%. Transient TSF activity (0-4 h) was only marginally influence d, while sustained TSF activity (8-24 h) was markedly reduced. TSF act ivity at 24 h correlated with peak TNF levels. IL-10 levels, coincidin g with early TSF activity, remained unchanged by anti-TNF treatment. L evels of active TGF-beta and the drop in latent TGF-beta were decrease d. We conclude that anti-TNF treatment reduces sustained TSF activity and may partially restore impaired cell-mediated immune function.