INTERLEUKIN-10 IS DOWN-REGULATED IN MONONUCLEAR-CELLS FROM ENDOTOXIN TOLERANT HUMANS

It has been shown that induction of endotoxin tolerance results in a d ecreased potential to produce proinflammatory cytokines such as TNF or IL-l. The present study was carried out to examine the capacity of pe ripheral blood mononuclear cells (PBMC) from endotoxin tolerant humans to synthesize the anti-inflammatory cytokines IL-10 and TGF beta in r esponse to endotoxin. Four individuals were rendered endotoxin toleran t by daily i.v. injections of endotoxin. PBMC were isolated before tol erance induction and on day 4 after the last endotoxin treatment. The cells were stimulated with endotoxin ex vivo and cytokines in culture supernatants were determined. PBMC isolated on day 4 of ail of the vol unteers showed decreased TNF alpha, IL-6 and IL-10 synthesis upon endo toxin treatment in vitro compared to pretolerant cells, while no diffe rences occurred with regard to the amount of TGF beta formed by PBMC b efore and after tolerance induction. Furthermore, no changes were foun d in the expression of HLA-DR on PBMC after tolerance induction.