Generation of inflammatory cytokines in zymosan-induced pleurisy in rats: TNF induces IL-6 and cytokine-induced neutrophil chemoattractant (CINC) in vivo

Levels of inflammatory cytokines tumour necrosis factor (TNF), interleukin 1 (LL-l), IL-6, and cytokine-induced neutrophil chemoattractant (CINC), whi ch is a member of the alpha-chemokine family in rats, were measured in the pleural exudates during zymosan-induced pleurisy to examine the relationshi p between the local production of cytokines and the inflammatory reaction. All four cytokine levels in the pleural exudate began to increase after 1-2 h, preceding the influx of neutrophils, and peaked after 4-5 h, Thereafter , these cytokine levels declined after 24 h, whereas the exudate volume sti ll continued to increase and leukocyte number reached a plateau, Concomitan t injection of actinomycin D (10 mu g) with zymosan markedly suppressed the neutrophil infiltration, parallel with CINC production in the pleural exud ate at 4 h, A transient elevation of IL-6 level, peaking at 5 h, and subseq uent rise in the level of an acute-phase protein, T-kininogen, were also ob served in the plasma. When recombinant human TNF-alpha (rhTNF-alpha) (20 00 0 U) was intrapleurally injected a rapid increase in pleural: CINC level, f ollowed by neutrophil infiltration, and a sharp rise in IL-6 level in the p lasma, followed by an increase in T-kininogen, were demonstrated. These res ults suggest that CINC produced in the pleural exudate may participate in n eutrophil infiltration, that IL-6 induced in the plasma stimulates T-kinino gen production, and that endogenous TNF may be partly involved in the induc tion of CINC and IL-6 in this zymosan inflammation. (C) 1998 Academic Press .