Endotoxin tolerance 유도상태에서 리포폴리사카라이드로 유도된 염증성 매개 인자의 in vitro 생산에 있어서 저농도 corticosterone 전처리 효과

Effect of Low Dose Corticosterone Pretreatment on the Production of LPS-Induced Inflammatory Mediators in Endotoxin-Preexposed Cells

Low dose glucocorticoids (GCs) are known to have proinflammatory effects in the LPS-stimulated innate immune cells. To investigate whether preconditioning of low dose corticosterone enhances or not LPS-induced production of inflammatory mediators and heper T (Th) cytokines in endotoxin tolerant cells (ET), RAW 264.7 cells and EL4 cells were pretreated with low dose corticosterone (Cort: 50 and 100 ng/ml) and low dose LPS (50 ng/ml) in fresh complete medium once a day for 3 days and then cultured in fresh complete medium for 6 hr or 24 hr in the presence or absence of LPS (1~10 μg/ml) or Con A. In the present study, the results demonstrated that Cort pretreatment strongly enhanced LPSinduced production of TNF-α, IL-6, IL-10, PGE 2 and NO by RAW 264.7 cells in a dose-dependent manner in control, whereas Cort pretreatment didn’t affect LPS-induced production of TNF-α, IL-10, PGE 2 but significantly enhanced LPS-induced production of IL-6 and NO in ET. Cort pretreatment strongly augmented Con A-induced- production of IFN-γ and IL-10 and ratios of IFN-γ/IL-10 by EL4 cells in a dose-dependent manner in control, whereas Cort 50 ng/ml pretreatment remarkably decreased Con A-induced production of IL-10 and ratios of IFN-γ/IL-10 in ET. Cort pretreatment strongly enhanced LPSinduced production of IFN-γ and IL-10 and attenuated ratios of IFN-γ/IL-10 by EL4 cells in control, whereas Cort pretreatment didn’t affect LPS-induced production of IFN-γ and IL-10 and enhanced ratios of IFN-γ/IL-10 in ET. These findings suggest that preconditioning of low dose corticosterone may enhance production of IL-6 and NO with a shift in the Th1/Th2 balance toward Th1 to secondary infection in a state of endotoxin tolerance, which may lead to low grade inflammation.