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 complement 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 cytokine release was evaluated in 17 baboons. All animals received 5 x 10(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-antibody, and seven received an infusion of 6 mg per kg body weight of HWA 138 in addition to the bacteria.


RESULTS
In baboons receiving 5 x 10(8) live E coli per kg body weight increased plasma levels of TCC, TNF-alpha and IL-8 were found. The release of TNF-alpha was lower in the group receiving HWA 138 at 2 h after the infusion. In baboons receiving an 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.


CONCLUSIONS
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.
Bengtsson
A
A
Department of Anaesthesiology & Intensive Care, Sahlgrenska University Hospital, Göteborg, Sweden.
Redl
H
H
Schlag
G
G
Mollnes
T E
TE
Högåsen
K
K
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D003167:Complement Activation; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D004927:Escherichia coli Infections / Q000276:immunology / Q000503:physiopathology; D006439:Hemodynamics; D016209:Interleukin-8 / Q000096:biosynthesis*; D008297:Male; D010215:Papio; D010431:Pentoxifylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D018805:Sepsis / Q000276:immunology* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology; D014970:Xanthines / Q000494:pharmacology
D000906:Antibodies; D015938:Complement Membrane Attack Complex; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D014970:Xanthines; C062028:1-(5-hydroxy-5-methylhexyl)-3-methylxanthine; D010431:Pentoxifylline