Mediratta P K, Bhatia J, Tewary S, Katyal V, Mahajan P, Sharma K K
Department of Pharmacology, University College of Medical Sciences & GTB Hospital, Delhi 110 095.
Indian J Physiol Pharmacol. 2003 Jul;47(3):288-96.
The present study investigates the effect of progesterone, a pregnane precursor of neurosteroids, and 4'-chlordiazepam (4'-CD), a specific ligand for mitochondrial diazepam binding inhibitor receptor (MDR) involved in neurosteroidogenesis, on restraint stress (RS)-induced modulation of humoral and cell-mediated immune responses. RS produced a significant reduction in anti-sheep red blood cells (SRBC) antibody titre, a measure of humoral immune response, and % leucocyte migration inhibition (LMI) and foot-pad thickness test, measures of cell-mediated immune responses. These effects of RS on immune responses were effectively blocked by pretreating the animals with progesterone (10 mg/kg, sc) or 4'-CD (0.5 mg/kg, sc) administered just before subjecting the animal to RS. The effect of both progesterone and 4'-CD on RS-induced immune modulation was significantly attenuated by bicuculline (2 mg/kg, ip) but not by flumazenil (10 mg/kg, ip). Unlike its effect on RS-induced immune responsiveness, progesterone (5, 10 mg/kg, sc) when administered to non-stressed animals produced a significant suppression of both humoral and cell-mediated immune responses which was not reversed by bicuculline. However, 4'-CD failed to modulate immune response in naive non-stressed animals. These results suggest that progesterone and 4'-CD affect stress-induced immune responses by modulating GABA-ergic mechanism. However, GABA-A receptor system does not appear to be involved in progesterone-induced immunosuppression in nonstressed animals.
本研究调查了孕酮（一种神经甾体的孕烷前体）和4'-氯地西泮（4'-CD，一种参与神经甾体生成的线粒体地西泮结合抑制受体（MDR）的特异性配体）对束缚应激（RS）诱导的体液免疫和细胞介导免疫反应调节的影响。RS显著降低了抗绵羊红细胞（SRBC）抗体滴度（一种体液免疫反应的指标）以及白细胞迁移抑制率（%LMI）和足垫厚度测试值（细胞介导免疫反应的指标）。在对动物施加RS之前，预先用孕酮（10mg/kg，皮下注射）或4'-CD（0.5mg/kg，皮下注射）处理动物，可有效阻断RS对免疫反应的这些影响。孕酮和4'-CD对RS诱导的免疫调节作用均被荷包牡丹碱（2mg/kg，腹腔注射）显著减弱，但未被氟马西尼（10mg/kg，腹腔注射）减弱。与对RS诱导的免疫反应性的影响不同，孕酮（5、10mg/kg，皮下注射）给予非应激动物时，会显著抑制体液免疫和细胞介导免疫反应，且这种抑制作用不会被荷包牡丹碱逆转。然而，4'-CD未能调节未受应激的正常动物的免疫反应。这些结果表明，孕酮和4'-CD通过调节γ-氨基丁酸能机制影响应激诱导的免疫反应。然而，γ-氨基丁酸A受体系统似乎不参与非应激动物中孕酮诱导的免疫抑制作用。
