Monoclonal antibody to tumor necrosis factor-alpha attenuates plasma interleukin-6 levels in porcine gram-negative sepsis.

This study examined the kinetics of IL-6 release into the systemic circulation in a porcine model of bacterial sepsis induced by infusion of live Pseudomonas aeruginosa. Three groups of animals were studied. Group I (n = 12) animals received a 1 hr infusion of live P. aeruginosa. Group II (n = 6) animals received monoclonal antibody to tumor necrosis factor-alpha (TNF-alpha) (15 mg/kg) prior to induction of sepsis. Group III (n = 7) animals received sterile saline only. TNF-alpha and interleukin-6 (IL-6) levels rose sharply, in group I following pseudomonas infusion. Following a peak at 120 min after the bacterial infusion (4.8 +/- 0.7 U/ml at 120 min vs 0.4 +/- 0.2 U/ml at 0 min), TNF-alpha levels subsequently declined prior to the end of the experiment. In contrast, IL-6 levels rose sharply, subsequent to TNF-alpha, peaked at 180 min, and remained significantly elevated throughout the study period (5.3 +/- 0.9 ng/ml vs 0.05 +/- 0.01 ng/ml, 0 min). In animals pretreated with monoclonal antibody to TNF-alpha, no increase in TNF-alpha activity was detected at any time during the period of study. IL-6 levels in antibody-treated animals, although greatly attenuated, still rose significantly above baseline (2.02 +/- 0.8 ng/ml at 180 min vs 0.05 +/- 0.01 ng/ml at 0 min) and above levels in control animals. We conclude that although TNF-alpha plays an important role in synthesis and release of IL-6, there is a TNF-alpha-independent pathway for release of IL-6 in sepsis.