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 effect on inhibition of IL-6 by HC. In contrast, the conditions of Mo culture had a significant impact on the kinetics of IL-6 production and inhibition by HC. Adherent Mo produced significantly higher levels of IL-6 4 hr after LPS compared to limited-adherent Mo. By 12 hr of LPS stimulation, comparable quantities of IL-6 were produced by both cultures. HC inhibition was complete 4 hr after LPS stimulation of adherent Mo, while 12 hr was required for maximum inhibition of limited-adherent Mo. Production of an IL-6 inhibitor was not responsible for the increased inhibition by HC with adherence, because both IL-6 protein and bioactivity were comparably decreased. The kinetics of inhibition of TNF alpha and IL-1 beta production by HC were similarly affected by adherence. Phenotypic analysis of cultured vs freshly isolated Mo showed a decrease in Mo expressing CD14, but not CD11b, which paralleled a decrease in IL-6 production by the cultured Mo. However, there were no phenotypic differences between adherent and limited-adherent Mo. The results 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.
Breuninger
L
L
Department of Microbiology and Immunology, Medical College of Pennsylvania, Philadelphia 19129.
Goonewardene
I M
IM
Dempsey
W L
WL
Murasko
D M
DM
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004347:Drug Interactions; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D010641:Phenotype; D013997:Time Factors; D000093242:Interleukin-6 Inhibitors
D006854:Hydrocortisone; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000093242:Interleukin-6 Inhibitors