Lauw F N, Dekkers P E, te Velde A A, Speelman P, Levi M, Kurimoto M, Hack C E, van Deventer S J, van der Poll T
Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
J Infect Dis. 1999 Mar;179(3):646-52. doi: 10.1086/314636.
To determine in vivo effects of interleukin (IL)-12 on host inflammatory mediator systems, 4 healthy chimpanzees received recombinant human IL-12 (1 microg/kg) by intravenous injection. IL-12 induced increases in plasma concentrations of IL-15, IL-18, and interferon-gamma (IFN-gamma), plus a marked antiinflammatory 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 chemoattractant protein-1, macrophage inflammatory protein-1beta). In addition, IL-12 elicited neutrophilic leukocytosis, neutrophil degranulation (elastase-alpha1-antitrypsin complexes), coagulation activation (F1 + 2 prothrombin fragment, thrombin-antithrombin III complexes), and fibrinolytic activation (tissue-type plasminogen activator, plasmin-alpha2-antiplasmin complexes). IL-12-induced activation of multiple host mediator systems was found only after 8-24 h, remained detectable until the end of the 48-h observation period, and occurred in the absence of detectable TNF and IL-1beta. These data may contribute to understanding the role of IL-12 in the pathogenesis of sepsis syndrome and the toxicity found after repeated injections of IL-12.
为了确定白细胞介素（IL）-12对宿主炎症介质系统的体内作用，4只健康黑猩猩通过静脉注射接受重组人IL-12（1微克/千克）。IL-12可诱导IL-15、IL-18和干扰素-γ（IFN-γ）血浆浓度升高，同时引发显著的抗炎细胞因子反应（IL-10、可溶性肿瘤坏死因子 [TNF] 受体、IL-1受体拮抗剂）以及α趋化因子（IL-8、IFN-γ诱导蛋白10）和β趋化因子（单核细胞趋化蛋白-1、巨噬细胞炎性蛋白-1β）的分泌。此外，IL-12可引起嗜中性白细胞增多、嗜中性粒细胞脱颗粒（弹性蛋白酶-α1抗胰蛋白酶复合物）、凝血激活（F1 + 2凝血酶原片段、凝血酶-抗凝血酶III复合物）以及纤溶激活（组织型纤溶酶原激活剂、纤溶酶-α2抗纤溶酶复合物）。仅在8 - 24小时后才发现IL-12诱导的多种宿主介质系统激活，在48小时观察期结束前均可检测到，且在未检测到TNF和IL-1β的情况下发生。这些数据可能有助于理解IL-12在脓毒症综合征发病机制中的作用以及重复注射IL-12后出现的毒性。
