Nockher W A, Scherberich J E
Laboratory of Immunology and Molecular Physiology, Department of Medicine IV, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
J Immunol. 1997 Feb 1;158(3):1345-52.
The effect of glucocorticoid (GC) treatment on expression and release of the monocyte cell surface LPS receptor Ag CD14 was studied in vivo and in vitro. In patients with acute inflammatory diseases receiving GC pulse therapy serum concentrations of soluble CD14 and CD14 expression by peripheral blood monocytes decreased significantly. The LPS-binding capacity correlated positively with the amount of cell surface CD14 by human blood monocytes. In vitro, a time- and dose-dependent effect of GC preparations on monocyte membrane and soluble CD14 by cultured peripheral blood monocytes was found. Incubation with 2 x 10(-8) M prednisolone down-regulated cell surface CD14 after 72 h, and 2 x 10(-7) M suppressed CD14 expression even after 24 h. Prednisolone also decreased release of the soluble CD14 Ag, where a 10-fold higher GC concentration was required for a significant suppression compared with membrane CD14 during culture. Expression of other monocyte membrane Ags were either unchanged (CD33, CD35), diminished (CD13, CD89), or increased (CD32) by GC, indicating no general down-modulation of cell surface Ag expression. Preincubation with glucocorticoids for 24 h significantly down-regulated CD14 expression during subsequent steroid-free culture for at least 7 days. In cultured monocytes, the LPS-induced increase of membrane and soluble CD14 was markedly but not completely inhibited by prednisolone. Therefore, GC treatment suppresses the up-regulation of the LPS receptor during endotoxin challenge, and likewise, the IL-1 secretion after LPS stimulus was significantly diminished. Taken together, the suppression of the monocytic cell surface and soluble endotoxin receptor CD14 by GC may contribute to the increased risk of infections in patients undergoing steroid therapy.
研究了糖皮质激素（GC）治疗对单核细胞表面脂多糖受体抗原CD14表达和释放的体内及体外作用。在接受GC冲击疗法的急性炎症性疾病患者中，可溶性CD14的血清浓度及外周血单核细胞的CD14表达显著降低。人血单核细胞的脂多糖结合能力与细胞表面CD14的量呈正相关。在体外，发现GC制剂对培养的外周血单核细胞的单核细胞膜及可溶性CD14具有时间和剂量依赖性效应。与2×10⁻⁸ M泼尼松龙孵育72小时后，细胞表面CD14下调，而2×10⁻⁷ M即使在24小时后也能抑制CD14表达。泼尼松龙还降低了可溶性CD14抗原的释放，与培养期间膜CD14相比，显著抑制需要高10倍的GC浓度。其他单核细胞膜抗原的表达要么未改变（CD33、CD35），要么减少（CD13、CD89），要么增加（CD32），表明细胞表面抗原表达无普遍下调。用糖皮质激素预孵育24小时可在随后至少7天的无类固醇培养期间显著下调CD14表达。在培养的单核细胞中，泼尼松龙可显著但不完全抑制脂多糖诱导的膜及可溶性CD14增加。因此，GC治疗在内毒素攻击期间抑制脂多糖受体的上调，同样，脂多糖刺激后的白细胞介素-1分泌也显著减少。综上所述，GC对单核细胞表面及可溶性内毒素受体CD14的抑制可能导致接受类固醇治疗患者感染风险增加。
