Hernandez-Pando R, de la Luz Streber M, Orozco H, Arriaga K, Pavon L, Marti O, Lightman S L, Rook G A
Department of Pathology, Instituto Nacional de la Nutricion, Salvador Zubiran, Mexico City.
QJM. 1998 Nov;91(11):755-66. doi: 10.1093/qjmed/91.11.755.
In Balb/c mice with pulmonary tuberculosis, there is a switch from a protective Th1-dominated cytokine profile to a non-protective profile with a Th2 component. This switch occurs while the adrenals are undergoing marked hyperplasia. Treatment with the anti-glucocorticoid hormones dehydroepiandrosterone or 3 beta, 17 beta-androstenediol, during the period of adrenal hyperplasia, maintains Th1 dominance and is protective. We investigated the effects of these hormones as therapeutic agents by administering them from day 60, when the switch to the non-protective cytokine profile was already well established. Given at this time (day 60), doses that were protective when given early (from day 0) were rapidly fatal. A physiological dose of the glucocorticoid corticosterone was also rapidly fatal. However when the corticosterone and the anti-glucocorticoid (AED or DHEA) were co-administered, there was protection, with restoration of a Th1-dominated cytokine profile, enhanced DTH responses, and enhanced expression of IL-1 alpha and TNF alpha. Therefore this combination of steroids has an emergent property that is quite unlike that of either type of steroid given alone. It may be possible to exploit the ant-inflammatory properties of glucocorticoids while preserving a Th1 bias, by combining glucocorticoids with DHEA or suitable metabolites.
在患有肺结核的Balb/c小鼠中，细胞因子谱从以保护性Th1为主转变为具有Th2成分的非保护性谱。这种转变发生在肾上腺明显增生期间。在肾上腺增生期间，用抗糖皮质激素脱氢表雄酮或3β,17β-雄烯二醇治疗，可维持Th1优势并具有保护作用。我们通过从第60天开始给药来研究这些激素作为治疗剂的效果，此时向非保护性细胞因子谱的转变已经确立。在这个时候（第60天）给予早期（从第0天开始）具有保护作用的剂量会迅速致命。生理剂量的糖皮质激素皮质酮也会迅速致命。然而，当同时给予皮质酮和抗糖皮质激素（AED或DHEA）时，会有保护作用，Th1为主的细胞因子谱得以恢复，迟发型超敏反应增强，IL-1α和TNFα的表达增强。因此，这种类固醇组合具有一种与单独给予任何一种类固醇完全不同的新特性。通过将糖皮质激素与DHEA或合适的代谢物联合使用，有可能在保持Th1偏向的同时利用糖皮质激素的抗炎特性。
