Interleukin-12 induces sustained activation of multiple host inflammatory mediator systems in chimpanzees

To determine in vivo effects of interleukin (IL)-12 on host inflammatory me diator systems, 4 healthy chimpanzees received recombinant human IL-12 (1 m u g/kg) by intravenous injection, IL-12 induced increases in plasma concent rations of IL-15, IL-18, and interferon-gamma (IFN-gamma), plus a marked an tiinflammatory cytokine response (IL-10, soluble tumor necrosis factor[TNF] receptors, IL-1 receptor antagonist) and secretion of alpha-chemokines (IL -8, IFN-gamma-inducible protein 10) and beta-chemokines (monocyte chemoattr actant protein-1, macrophage inflammatory protein-1 beta). In addition, IL- 12 elicited neutrophilic leukocytosis, neutrophil degranulation (elastase-a lpha(1)-antitrypsin complexes), coagulation activation (F1 + 2 prothrombin fragment, thrombin-antithrombin III complexes), and fibrinolytic activation (tissue-type plasminogen activator, plasmin-alpha(2)-antiplasmin complexes ). IL-12-induced activation of multiple host mediator systems was found onl y after 8-24 h, remained detectable until the end of the 48-h observation p eriod, and occurred in the absence of detectable TNF and IL-1 beta. These d ata may contribute to understanding the role of IL-12 in the pathogenesis o f sepsis syndrome and the toxicity found after repeated injections of IL-12 .