Musabak U, Bolu E, Ozata M, Oktenli C, Sengul A, Inal A, Yesilova Z, Kilciler G, Ozdemir I C, Kocar I H
Department of Immunology, Gülhane School of Medicine, Ankara, Turkey.
Clin Exp Immunol. 2003 May;132(2):265-70. doi: 10.1046/j.1365-2249.2003.02141.x.
In the present study, we aimed to investigate the effects of testosterone deficiency and gonadotropin therapy on the in vitro production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) by peripheral blood mononuclear cells (PBMCs) from patients with idiopathic hypogonadotropic hypogonadism (IHH) in order to elucidate the modulatory role of androgen in cytokine production. Fifteen male patients with untreated IHH and 15 age-matched healthy male subjects were enrolled in the study. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), free testosterone (FT), sex hormone binding globulin (SHBG), prolactin, and IL-2 and IL-4 levels were also measured. In unstimulated cultures, IL-1beta and TNF-alpha secretion were not significantly different between patient and control groups. However, after stimulation with lipopolysaccharide (LPS), secretion of IL-1beta and TNF-alpha was significantly higher in cultures from untreated patients with IHH than in control subjects. Mean FSH, LH and FT levels were significantly lower, whereas SHBG, IL-2 and IL-4 levels were significantly higher in patients with IHH compared than in controls. In patients with IHH, FT negatively affected the serum levels of IL-4 and in vitro secretion of IL-1beta and TNF-alpha. In addition, IL-2 and IL-4 affected the in vitro secretion of IL-1beta in a positive manner. Gonadotropin therapy decreased both TNF-alpha and IL-1beta in PBMCs from patients with IHH. The levels of serum IL-2 and IL-4 were also decreased by therapy. In conclusion, in the present study, gonadotropin treatment restored the in vitro production of IL-1beta and TNF-alpha by PBMCs from patients with IHH, suggesting that androgen modulates proinflammatory cytokine production, at least directly through its effects on PBMCs. It seems probable that this effect plays an important role in the immunosuppressive action of androgens.
在本研究中，我们旨在调查睾酮缺乏和促性腺激素治疗对特发性低促性腺激素性性腺功能减退（IHH）患者外周血单个核细胞（PBMC）体外产生肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的影响，以阐明雄激素在细胞因子产生中的调节作用。15例未经治疗的IHH男性患者和15例年龄匹配的健康男性受试者纳入本研究。同时还检测了血清促卵泡生成素（FSH）、促黄体生成素（LH）、游离睾酮（FT）、性激素结合球蛋白（SHBG）、催乳素以及IL-2和IL-4水平。在未刺激的培养物中，患者组和对照组之间IL-1β和TNF-α的分泌无显著差异。然而，用脂多糖（LPS）刺激后，未经治疗的IHH患者培养物中IL-1β和TNF-α的分泌显著高于对照组。与对照组相比，IHH患者的平均FSH、LH和FT水平显著降低，而SHBG、IL-2和IL-4水平显著升高。在IHH患者中，FT对IL-4的血清水平以及IL-1β和TNF-α的体外分泌产生负面影响。此外，IL-2和IL-4对IL-1β的体外分泌有正向影响。促性腺激素治疗降低了IHH患者PBMC中TNF-α和IL-1β的水平。治疗后血清IL-2和IL-4水平也降低。总之，在本研究中，促性腺激素治疗恢复了IHH患者PBMC体外产生IL-1β和TNF-α的能力，提示雄激素至少直接通过其对PBMC的作用调节促炎细胞因子的产生。这种作用可能在雄激素的免疫抑制作用中起重要作用。
