van Deuren M
Department of Internal Medicine, University Hospital Nijmegen, The Netherlands.
Eur J Clin Microbiol Infect Dis. 1994;13 Suppl 1:S12-6. doi: 10.1007/BF02390680.
Tumour necrosis factor-alpha (TNF) and interleukin-1 beta (IL-1 beta) are the central mediators in the genesis of sepsis. The proinflammatory effects of these cytokines are counteracted in vivo by natural inhibitors. Soluble TNF receptors (sTNFR) are shed upon inflammatory stimuli such as IL-1 beta and TNF itself. Circulating TNF can be complexed by these receptors, thus preventing TNF from binding to effector cells. The binding of IL-1 beta to its receptor can be blocked by high concentrations of interleukin-1 receptor antagonist (IL-1Ra), which is produced and released upon nearly the same stimuli as IL-1 beta. This review presents some aspects of the kinetic behaviour of native sTNFR and of the production of native IL-1Ra during severe infections. It appears that in fulminant septicaemia, the plasma concentration of TNF is increased only transiently, during the very early stage of the infection. The concentration of sTNFR, in contrast, remains elevated much longer, probably due to a slower clearance. During the acute stage of severe infectious diseases, peripheral blood cells cannot be stimulated to produce IL-1 beta. The production of IL-1 Ra, in contrast, is not affected. Thus, the kinetic behaviour and regulation of TNF and IL-1 beta, is different from that of their antiinflammatory counterparts.
肿瘤坏死因子-α（TNF）和白细胞介素-1β（IL-1β）是脓毒症发生过程中的核心介质。这些细胞因子的促炎作用在体内会被天然抑制剂抵消。可溶性TNF受体（sTNFR）在诸如IL-1β和TNF自身等炎症刺激下会脱落。循环中的TNF可与这些受体结合形成复合物，从而阻止TNF与效应细胞结合。高浓度的白细胞介素-1受体拮抗剂（IL-1Ra）可阻断IL-1β与其受体的结合，IL-1Ra与IL-1β在几乎相同的刺激下产生并释放。本综述介绍了严重感染期间天然sTNFR的动力学行为以及天然IL-1Ra产生的一些方面。在暴发性败血症中，TNF的血浆浓度似乎仅在感染的极早期短暂升高。相比之下，sTNFR的浓度升高的时间要长得多，这可能是由于清除较慢。在严重传染病的急性期，外周血细胞无法被刺激产生IL-1β。相比之下，IL-1Ra的产生不受影响。因此，TNF和IL-1β的动力学行为及调节与其抗炎对应物不同。
