EFFECTS ON COMPLEMENT ACTIVATION AND CYTOKINE (TNF-ALPHA AND IL-8) RELEASE OF INFUSION OF ANTI-TNF-ANTIBODIES OR A XANTHINE DERIVATIVE (HWA-138) IN SEPTIC BABOONS

Background. Sepsis and septic shock lead to activation of the compleme nt cascade and to the release of pro-inflammatory cytokines. Methods. The effects of E coli infusion and of infusion of anti-TNF antibodies and a xanthine derivative (HWA 138) on complement activation and cytok ine release was evaluated in 17 baboons. All animals received 5X10(8) live bacteria per kg body weight. Five animals received only bacteria, five received in addition 0.5 mg per kg body weight of anti-TNF-antib ody, and seven received an infusion of 6 mg per kg body weight of HWA 138 in addition to the bacteria. Results. in baboons receiving 5X10(8) live E coli per kg body weight increased plasma levels of TCC, TNF-al pha and IL-8 were found. The release of TNF-alpha was lower in the gro up receiving HWA 138 at 2 h after the infusion. In baboons receiving a n infusion of anti-TNF antibody the concentration of IL-8 was lower at 2 and 4 h than in animals receiving just E coli or HWA 138. Conclusio n. Infusion of anti-TNF-antibody before E coli infusion will decrease the formation of IL-8. Infusion of HWA 138 before the E coli infusion will also inhibit the formation of TNF-alpha.