Šterzl I, Hill M, Stárka L, Velíková M, Kančeva R, Jemelková J, Czerneková L, Kosztyu P, ZadraŽil J, Matoušovic K, Vondrák K, Raška M
Institute of Endocrinology, Prague, Czech Republic.
Physiol Res. 2017 Sep 26;66(Suppl 3):S433-S442. doi: 10.33549/physiolres.933732.
Glucocorticoid (GC) therapy is one of the methods of choices for treatment of autoimmune diseases (ADs). In addition, adrenal androgens are known as immunoprotective GC-antagonists. Adrenal steroids preferentially influence the Th1-components over the Th2 ones. We investigated steroid metabolome (using gas chromatography-mass spectrometry) in healthy controls (H), GC-untreated patients with ADs different from IgA nephropathy (U), GC-treated patients with ADs different from IgA nephropathy (T) and in patients with IgA nephropathy (IgAN), which were monitored on the beginning (N0), after one week (N1) and after one month (N2) of prednisolone therapy (60 mg of prednisolone/day/m(2) of body surface). Between-group differences were assessed by one-way ANOVA, while the changes during the therapy were evaluated by repeated measures ANOVA. The ANOVA testing was followed by Duncan's multiple comparisons. IgAN patients and patients with other ADs exhibited lack of adrenal androgens due to attenuated activity of adrenal zona reticularis (ZR). Androgen levels including their 7alpha-, 7beta-, and 16alpha-hydroxy-metabolites were further restrained by GC-therapy. Based on these results and data from the literature, we addressed the question, whether a combination of GCs with delta(5)-steroids or their more stable synthetic derivatives may be optimal for the treatment of antibodies-mediated ADs.
糖皮质激素(GC)疗法是治疗自身免疫性疾病(ADs)的首选方法之一。此外,肾上腺雄激素被认为是具有免疫保护作用的GC拮抗剂。肾上腺类固醇对Th1成分的影响优先于Th2成分。我们使用气相色谱-质谱法研究了健康对照者(H)、未接受GC治疗的非IgA肾病ADs患者(U)、接受GC治疗的非IgA肾病ADs患者(T)以及IgA肾病(IgAN)患者的类固醇代谢组,这些患者在泼尼松龙治疗开始时(N0)、治疗一周后(N1)和治疗一个月后(N2)接受监测(泼尼松龙剂量为60mg/天/体表平方米)。组间差异通过单因素方差分析进行评估,而治疗期间的变化通过重复测量方差分析进行评估。方差分析测试后进行邓肯多重比较。IgAN患者和其他ADs患者由于肾上腺网状带(ZR)活性减弱而表现出肾上腺雄激素缺乏。GC治疗进一步抑制了雄激素水平,包括其7α-、7β-和16α-羟基代谢产物。基于这些结果和文献数据,我们提出了一个问题,即GC与δ5-类固醇或其更稳定的合成衍生物联合使用是否可能是治疗抗体介导的ADs的最佳方案。