Welker P, Lippert U, Nürnberg W, Krüger-Krasagakes S, Möller A, Czarnetzki B M
Department of Dermatology, Virchow Clinics of Humboldt University, Berlin, Germany.
Int Arch Allergy Immunol. 1996 Feb;109(2):110-5. doi: 10.1159/000237208.
Since glucocorticoid effects on inflammatory processes may be mediated via modulation of cytokine release, different types of myelomonocytic cells were stimulated in vitro with lipopolysaccharide (50 ng/ml) or phorbol myristate acetate (25 ng/ml) plus the ionophore A23187, 2 x 10(-7) M, and release of interleukin (IL)-1 beta, IL-8 and tumor necrosis factor (TNF)-alpha was measured after 24 h by ELISA. Peripheral blood mononuclear cells from two allergic and two normal human donors released similarly large quantities of IL-8 and lower amounts of IL-1 beta and TNF-alpha. This also held for myelomonocytic cell lines, with THP-1 cells being most active, followed by U-937 and HL-60 cells. All potent glucocorticoids studied caused a dose-dependent inhibition of cytokine release from donor cells, being most marked for IL-1 beta and lowest for IL-8. Inhibition of cytokine release was also noted with U-937 cells, with clear differences in potency between the glucocorticoids, whereas release was enhanced in all experiments with THP-1 cells. These results were confirmed with Northern blot analysis. Modulating effects of glucocorticoids on cytokine release are thus complex, and are particularly dependent on the cell type studied.
由于糖皮质激素对炎症过程的影响可能是通过调节细胞因子的释放来介导的，因此，分别用脂多糖（50 ng/ml）或佛波醇肉豆蔻酸酯乙酸盐（25 ng/ml）加离子载体A23187（2×10⁻⁷ M）在体外刺激不同类型的骨髓单核细胞，24小时后通过酶联免疫吸附测定法（ELISA）检测白细胞介素（IL）-1β、IL-8和肿瘤坏死因子（TNF）-α的释放。来自两名过敏患者和两名正常人类供体的外周血单核细胞释放出相似大量的IL-8以及较少量的IL-1β和TNF-α。骨髓单核细胞系也是如此，THP-1细胞最为活跃，其次是U-937和HL-60细胞。所研究的所有强效糖皮质激素均导致供体细胞释放细胞因子受到剂量依赖性抑制，对IL-1β的抑制最为明显，对IL-8的抑制最低。在U-937细胞中也观察到细胞因子释放受到抑制，不同糖皮质激素之间的效力存在明显差异，而在所有用THP-1细胞进行的实验中，细胞因子释放均增强。这些结果通过Northern印迹分析得到证实。因此，糖皮质激素对细胞因子释放的调节作用是复杂的，并且特别依赖于所研究的细胞类型。
