KINETICS OF TUMOR-NECROSIS-FACTOR-ALPHA, SOLUBLE TUMOR-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 proinflammator y effects of these cytokines are counteracted in vivo by natural inhib itors. Soluble TNF receptors (sTNFR) are shed upon inflammatory stimul i such as IL-1 beta and TNF itself. Circulating TNF can be complexed b y these receptors, thus preventing TNF from binding to effector cells. The binding of IL-1 beta to its receptor can be blocked by high conce ntrations of interleukin-1 receptor antagonist (PL-1Ra), which is prod uced and released upon nearly the same stimuli as IL-1 beta. This revi ew presents some aspects of the kinetic behaviour of native sTNFR and of the production of native IL-1Ra during severe infections. It appear s that in fulminant septicaemia, the plasma concentration of TNF is in creased only transiently, during the very early stage of the infection . The concentration of sTNFR, in contrast, remains elevated much longe r, probably due to a slower clearance. During the acute stage of sever e infectious diseases, peripheral blood cells cannot be stimulated to produce IL-1 beta. The production of IL-1Ra, in contrast, is not affec ted. Thus, the kinetic behaviour and regulation of TNF and IL-1 beta, is different from that of their antiinflammatory counterparts.