MONOCYTE CULTURE AND ADHERENCE MODIFIES LPS-INDUCED IL-6 PRODUCTION AND INHIBITION BY HYDROCORTISONE

The effect of hydrocortisone (HC) on IL-6 production by monocytes (Mo) that were cultured under either adherent or limited-adherent culture conditions was determined. Although freshly isolated Mo produced more IL-6 in response to LPS than Mo cultured 24 hr, culture had little eff ect on inhibition of IL-6 by HC. In contrast, the conditions of Mo cul ture had a significant impact on the kinetics of IL-6 production and i nhibition by HC. Adherent Mo produced significantly higher levels of I L-6 4 hr after LPS compared to limited-adherent Mo. By 12 hr of LPS st imulation, comparable quantities of IL-6 were produced by both culture s. HC inhibition was complete 4 hr after LPS stimulation of adherent M o, while 12 hr was required for maximum inhibition of limited-adherent Mo. Production of an IL-6 inhibitor was not responsible for the incre ased inhibition by HC with adherence, because both IL-6 protein and bi oactivity were comparably decreased. The kinetics of inhibition of TNF alpha and IL-1 beta production by HC were similarly affected by adher ence. Phenotypic analysis of cultured vs freshly isolated Mo showed a decrease in Mo expressing CD14, but not CD11b, which paralleled a decr ease in IL-6 production by the cultured Mo. However, there were no phe notypic differences between adherent and limited-adherent Mo. The resu lts demonstrate that the time of Mo culture, as well as adherence, may serve to alter LPS-induced IL-6 production and its inhibition by HC. (C) 1994 Academic Press, Inc.