Control of immunity and allergy by steroid hormones

Steroid hormones, especially glucocorticoids, androgens, and estrogens, have profound influence on immunity. Recent studies using cell-type specific steroid hormone receptor-deficient mice have revealed the precise roles of some of these hormones in the immune system. Glucocorticoids are known to have strong anti-inflammatory and immunosuppressive effects and pleiotropic effects on innate and adaptive immune responses. They suppress the production of inflammatory cytokines by macrophages and DCs and the production of IFN-γ by NK cells, thus inhibiting innate immunity. By contrast, glucocorticoids enhance the immune response by inducing the expression of IL-7R and CXCR4 in T cells and the accumulation of T cells in lymphoid organs in accordance with the diurnal change of the glucocorticoid concentration. Thus, glucocorticoids suppress innate immunity but enhance adaptive immunity. Androgens suppress the homeostasis and activation of ILC2s and the differentiation of Th2 and Th17 cells and enhance the suppressive function of Tregs, thereby alleviating allergic airway inflammation. Thus, these steroid hormones have pleiotropic functions in the immune system. Further investigations are awaited on the regulation of immunity and allergy by estrogens using cell-specific steroid hormone receptor-deficient mice.     

Morphine exposure prevents up-regulation of MR and GR binding sites in the brain of adult male and female rats due to prenatal stress

Our previous work demonstrated that the hormone response to stress and the negative feedback inhibition to these hormones are sex-dependently altered by prenatal morphine exposure in adult rats. An alteration in the glucocorticoid negative feedback inhibition is mediated by glucocorticoid receptors (GR) that are distributed throughout the brain, and mineralocorticoid receptors (MR) localized mainly in the hippocampus and involved in a tonic influence of brain functions. Therefore, the present study examined the binding characteristics of MR and GR in young adult male and female rats exposed prenatally (E11-E18) to morphine (10 mg/kg/2 x /day), saline or no treatment at all (controls). At 60-90 days of age, animals were adrenalectomized (ADX) 24 h prior to decapitation. The hippocampus and hypothalamus were dissected for saturation binding assays. The data demonstrate that prenatal stress due to maternal saline injections up-regulates MR and GR binding in the hippocampus of adult male rats and this effect is prevented by prenatal morphine exposure. There is no effect of prenatal morphine exposure on GR binding in the hypothalamus of males. In female rats, prenatal morphine exposure does not affect the binding of MR and GR in the hippocampus or GR in the hypothalamus relative to controls; however, they are affected by ovarian hormone fluctuation. Moreover, prenatal stress decreases MR binding in the hippocampus of diestrous females and GR binding in the hypothalamus of estrous females. Both decreases are prevented by prenatal morphine exposure. Thus, the present study demonstrates that: (1) prenatal stress due to maternal saline injections alters MR and GR binding of adult male and female rats and is prevented by prenatal morphine exposure; (2) the MR and GR binding in adult female rats are affected by ovarian hormone fluctuations.     

Effect of cortisone on cells at the bone-marrow interface

Summary A study of the association between the rate of proliferation of marrow fibroblast-like stromal cells (in vitro) and the rate of endosteal bone mineralization (EsMR) (in vivo) was undertaken in an osteopenic rat model. We report than 200 g male rats treated with cortisone acetate (5 mg/day for 7 days) exhibit decreases in marrow fibroblast colony-forming units (FCFU) and tetracycline-based measurements of EsMR at the level of the femoral midshaft. In cortisone-treated rats recovering for 1–3 weeks, the FCFU census and EsMR normalized during the first posttreatment week, remained at control levels after 2–3 weeks, and exhibited a relapse in the third week which signified only partial recovery. These changes were unrelated to patterns of body weight gain. The data indicate that the FCFU census can serve to index endosteal osteoblast vigor.     

免疫球蛋白联合鞘内注射激素治疗重症格林-巴利综合征

目的观察免疫球蛋白联合鞘内注射激素治疗重症格林-巴利综合征的疗效。方法应用Hughes量表评价疗效。结果治疗组起效时间明显短于对照组,治疗组Hughes临床分级评分改善明显优于对照组。结论免疫球蛋白联合鞘内注射激素治疗重症格林-巴利综合征可缩短病程、缓解急性期症状。     

非糖皮质激素的免疫抑制方案对同种异体移植胰岛的保护作用

目的　评价非糖皮质激素的免疫抑制方案对防止大鼠同种异体胰岛移植排斥反应的效果。方法　大鼠同种异体胰岛移植后 ,分别应用他克莫司 (FK5 0 6 ) 霉酚酸酯 (MMF)和FK5 0 6 MMF 泼尼松 (Pred)行免疫抑制治疗两周 ,并设对照组 ,动态观察受者血糖、胰岛素及C肽变化 ,并作移植部位的形态学检测。结果　FK5 0 6 MMF组和FK5 0 6 MMF Pred组与对照组相比 ,移植胰岛存活时间明显延长 ,移植后 2个月在受者肝汇管区可见较多形态完整的胰岛细胞。FK5 0 6 MMF组维持术后正常血糖、胰岛素及C肽的时间超过 6 0d ,而FK5 0 6 MMF Pred组与前者比较 ,分泌C肽较少 (P <0 .0 5 ) ,血糖维持在较高水平 (P <0 .0 1) ,胰岛素水平两组差异无显著性。FK5 0 6 MMF Pred组停药两周以后的血糖水平较用药期间、停药两周内有明显降低 (P <0 .0 5 ) ,胰岛素和C肽分泌有所增多 ,但差异无显著性。结论　应用FK5 0 6 MMF和FK5 0 6 MMF Pred均有很强的免疫抑制效应 ,但糖皮质激素对胰岛细胞有毒性作用。小剂量FK5 0 6与MMF联用对移植胰岛细胞有较强的保护作用。     

过氧化物酶体增殖物激活受体γC161T基因多态性与糖皮质激素性骨质疏松症的关系

目的 探讨中国人过氧化物酶体增殖物激活受体γ(PPARγ)基因外显子6 C161T多态性与糖皮质激素性骨质疏松症(GIO)的相关关系。方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RELP)方法测定208例正常健康人（Ⅰ组）、168例非GIO患者（Ⅱ组）和104例GIO患者（Ⅲ组）PPARγ基因外显子6 C161T的基因型。应用双能X线骨密度仪(DEXA)测定股骨、腰椎等部位的骨密度。 结果 外显子6 C161T有CC、CT、TT 3种基因型。GIO组CC基因型频率显著低于正常对照组；CT和TT基因型频率显著高于正常对照组。非GIO组、应用激素组（GIO组＋非GIO组）与正常对照组比较，各基因型频率差异均无统计学意义。正常对照组C161T的CC基因型组各部位的骨密度有高于CT和TT基因型组的趋势，但差异无统计学意义。非GIO组和GIO组C161T的CC基因型组腰椎的骨密度明显高于CT和TT基因型组 (P ＜ 0.05)，分别为非GIO组CC型（1.04±0.17） g/cm2，CT+TT型（1.02±0.07） g/cm2；GIO组CC型（0.94±0.12） g/cm2，CT+TT型（0.83±0.08） g/cm2。经年龄、体重指数等因素校正后，差异仍有统计学意义(P ＜ 0.05）。 结论 PPARγ基因C161T基因型在正常人和应用激素患者之间无明显差异，它可能与肾小球肾炎的发病无关。C161T基因型在GIO组和正常对照组之间差异有统计学意义，它可能与糖皮质激素性骨质疏松症的发病有关。PPARγ基因C161T多态性与应用糖皮质激素患者腰椎的骨密度有关。等位基因C可能是骨量的保护因子，它可能与应用糖皮质激素后骨量的丢失有关。     

Low peripheral plasma renin activity as a critical marker in pediatric hypertension

In evaluating hypertensive children and adolescents, the etiological considerations should include a set of inherited disorders that share very low plasma renin activity (PRA) as a common feature. In particular among these disorders, glucocorticoid remediable aldosteronism (GRA) appears to be emerging as an important etiology of hypertension in the pediatric population. We report the evaluation of a 9-year-old Caucasian girl who presented with severe hypertension and a strong family history of early-onset hypertension. Her suppressed PRA, her family history, and her failure to respond to conventional antihypertensive therapy raised GRA as a potential etiology. The diagnosis was confirmed by an elevated ratio of urinary 18-oxotetrahydrocortisol to urinary tetrahydroaldosterone and genetic testing, which demonstrated the chimeric gene duplication. The molecular pathogenesis of GRA and the clinical implications are reviewed. Received May 15, 1996; received in revised form and accepted September 16, 1996     

The effect of adrenalectomy on stress-induced c-fos mRNA expression in the rat brain

Previously, we determined the pattern of stress-induced c-fos mRNA expression throughout the brain in order to gain further insight into the identification of the neural circuits mediating stress-induced regulation of the hypothalamic-pituitary-adrenal axis. In the present study, we determined if rapid effects of increased glucocorticoid levels after stress contribute to changes in c-fos mRNA expression. To this end, stress-induced c-fos expression was characterized in adrenalectomized (ADX) or adrenalectomized and corticosterone replaced (ADX/B) male rats. Animals were sacrificed 30 min post-onset of a 10 min swim stress, and in situ hybridization histochemistry was used to detect c-fos mRNA throughout the brain. The pattern of c-fos induction in the ADX and ADX/B animals was similar to that observed in the sham operated animals. Additionally, densitometric measurements were made to quantify the c-fos response in the paraventricular nucleus of the hypothalamus and the CA1/2 region of the hippocampus. We found that ADX did not alter the magnitude of the c-fos response to stress in these areas, but there was a slight dampening of the response in ADX/B animals. In sum, these results suggest that the pattern of c-fos expression observed 30 min post-stress is independent of stress-induced increases in circulating glucocorticoid concentrations.     

糖皮质激素对肾小球疾病患者骨代谢影响因素的研究

目的　探讨长期应用糖皮质激素 (GC)治疗对肾小球疾病患者骨代谢影响的因素。方法　 2 0 7例肾小球疾病患者 ,应用常规剂量GC治疗 ,于治疗前及治疗后每隔 3～ 6个月 ,进行了 35 7例次腰椎和股骨近端骨密度 (BMD)、血钙、血磷和骨钙素浓度测定。结果　①用GC后骨钙素浓度明显降低 (P均 <0 0 0 5 ) ,但其不能预测BMD下降。②用药 15个月后男性各部位BMD均减少 (32 2～111 5 )mg/cm2 ,以L1 4和股骨粗隆更明显 (P均 <0 0 5 ) ,骨丢失率 3 3%～ 10 3% ;女性L1 4BMD均减少(4 3 8～ 76 0 )mg/cm2 ,以L1更明显 (P <0 0 5 ) ,骨丢失率 3 9%～ 7 9%。③年龄与各部位BMD变化呈负相关 ,但不影响GC造成的骨丢失。男性各部位、女性L1 4BMD减少与GC累计剂量和GC用药时间负相关。④用GC15个月 (GC累计剂量 10g以上 ) ,男性L1 4BMD正常的比例从 3/ 4至 3/ 5 ;女性L1和L2 BMD正常者从 3/ 4减少到 1/ 2。结论　长期口服糖皮激素导致与剂量和用药时间相关的腰椎和男性股骨粗隆骨丢失 ,年龄偏大和男性患者骨丢失更明显。     

糖皮质激素受体阻断对烫伤大鼠肺、肾血管壁通透性变化的影响

我们以糖皮质激素受体（ＧＲ）的竞争性拮抗剂ＲＵ３８４８６（简称ＲＵ４８６）阻断大鼠体内的ＧＲ，并通过检测肺、肾组织匀浆中荧光标记白蛋白的含量，观察了烫伤后１２ｈ大鼠肺、肾血管壁通透性的变化以及阻断ＧＲ对这种变化的影响。结果显示：烫伤后１２ｈ，大鼠肺、肾组织匀浆中荧光标记白蛋白含量明显高于对照组（肺：Ｐ＜０．０５；肾：Ｐ＜０．００１）；阻断ＧＲ后再烫伤大鼠，其肺、肾组织匀浆中的荧光白蛋白含量又显著高于烫伤组（Ｐ＜０．０５）。提示：①烫伤后１２ｈ，大鼠肺、肾血管壁通透性明显升高。②ＧＲ减少可加重烫伤所致的血管壁通透性升高，并可逆转内源性糖皮质激素（ＧＣ）稳定血管壁通透性的作用。