van Ierssel G J, Mieremet-Ooms M A, van der Zon A M, van Hogezand R A, Wagtmans M J, van der Sluys Veer A, Lamers C B, Verspaget H W
Department of Gastroenterology and Hepatology, University Hospital Leiden, The Netherlands.
Immunopharmacology. 1996 Sep;34(2-3):97-104. doi: 10.1016/0162-3109(96)00112-9.
Recently, we have shown that administration of adrenocorticotropic hormone (ACTH) to corticosteroid-treated Crohn's disease (CD) patients increased the peripheral blood natural killer (NK) cell activity which was suppressed by the corticosteroids. To elucidate this observation we analysed the in vitro effect of budesonide, prednisolone, cortisol, and ACTH on NK cells of healthy volunteers and corticosteroid-treated CD patients. Incubation of peripheral blood mononuclear cells (PBMNC) from healthy volunteers during the cytotoxicity assay caused a dose-dependent inhibition of NK cell activity by the three corticosteroids, while ACTH had hardly any effect. Pre-incubation for 18 h with high and low inhibiting concentrations also showed a significant inhibiting effect on NK cell activity of the corticosteroids. The percentage of CD56+ NK cells tended to increase after pre-incubation with a high inhibiting concentration of budesonide, prednisolone, and cortisol. Incubation of budesonide- or prednisolone-suppressed PBMNC from healthy volunteers and CD patients, with ACTH and/or cortisol, to mimic the in vivo situation, did not restore the corticosteroid-induced suppression of NK cell activity. The increase of the budesonide- or prednisolone-suppressed NK cell activity after in vivo administration of ACTH to the CD patients is therefore probably not a direct effect of cortisol or ACTH. Presumably other factors like cytokines and/or neurohormones must be involved in the in vivo interaction between corticosteroids, ACTH, and NK cells.
最近，我们发现，给接受皮质类固醇治疗的克罗恩病（CD）患者注射促肾上腺皮质激素（ACTH）可提高外周血自然杀伤（NK）细胞活性，而该活性此前被皮质类固醇抑制。为阐明这一现象，我们分析了布地奈德、泼尼松龙、皮质醇和ACTH对健康志愿者及接受皮质类固醇治疗的CD患者NK细胞的体外作用。在细胞毒性试验中，健康志愿者外周血单个核细胞（PBMNC）与三种皮质类固醇孵育会导致NK细胞活性出现剂量依赖性抑制，而ACTH几乎没有任何作用。用高、低抑制浓度预孵育18小时也显示皮质类固醇对NK细胞活性有显著抑制作用。用高抑制浓度的布地奈德、泼尼松龙和皮质醇预孵育后，CD56+NK细胞百分比有增加趋势。为模拟体内情况，将来自健康志愿者和CD患者的经布地奈德或泼尼松龙抑制的PBMNC与ACTH和/或皮质醇孵育，并未恢复皮质类固醇诱导的NK细胞活性抑制。因此，CD患者体内注射ACTH后，布地奈德或泼尼松龙抑制的NK细胞活性增加可能并非皮质醇或ACTH的直接作用。推测细胞因子和/或神经激素等其他因素一定参与了皮质类固醇、ACTH和NK细胞之间的体内相互作用。
