Kinetics of tumour necrosis factor-alpha, soluble tumour necrosis factor receptors, interleukin 1-beta and its receptor antagonist during serious infections.
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.
van Deuren
M
M
Department of Internal Medicine, University Hospital Nijmegen, The Netherlands.
D006801:Humans; D007239:Infections / Q000097:blood / Q000378:metabolism*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000097:blood*; D007700:Kinetics; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha