RELATION BETWEEN PROINFLAMMATORY AND ANTIINFLAMMATORY CYTOKINES AND THE PRODUCTION OF NITRIC-OXIDE (NO) IN SEVERE SEPSIS

The aim of the present study was to investigate the relationship betwe en the levels of pro-inflammatory [interleukin 6 (IL-6), IL-8, tumour necrosis factor alpha (TNF-alpha)], anti-inflammatory cytokines [IL-10 , soluble TNF receptor type I (TNFsrI), TNFsrII], and the production o f nitric oxide (NO) during a 1-week period in 23 patients with severe sepsis, The highest levels of pro-inflammatory cytokines and nitrate, the stable metabolite of NO, were found during the first day after inc lusion and gradually declined thereafter, Detectable levels of IL-10, TNFsrI and TNFsrII were present in all patients at study entry but did not significantly change during the study period [analysis of varianc e (MANOVA); P > 0.05], Serum nitrate levels correlated significantly w ith both pro-inflammatory cytokines (IL-6, IL-8, TNF-alpha) as well as anti-inflammatory cytokines (IL-10, TNFsrI, TNFsrII), Serum nitrate l evels over time were higher in patients with positive blood cultures ( n = 4) (MANOVA; P < 0.005), as compared to patients without proven bac teraemia. These data support the concept of an acute phase of sepsis t hat is characterized by an excess of pro-inflammatory cytokines, while anti-inflammatory cytokines are predominantly present during the seco ndary phase, The present findings indicate that pro-inflammatory cytok ines are related to the induction of excessive NO production during th e first phase of sepsis and that reduction of NO production occurs dur ing the secondary phase, This may suggest that anti-inflammatory cytok ines are able to diminish the production of NO in patients with severe sepsis. (C) 1997 Academic Press Limited.