ENDOCRINE MODULATION OF IMMUNE-MEDIATED EYE DISEASE IN RATS

大鼠免疫介导眼病的内分泌调节

• 批准号: 3898141
• 负责人: A G PALESTINE
• 金额: --
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3898141
• 关键词: antigens; autoimmune disorder; bromocriptine; cellular immunity; combination chemotherapy; cyclosporines; dosage; eye disorder chemotherapy; hormone regulation /control mechanism; humoral immunity; immunomodulators; immunopharmacology; immunoregulation; immunosuppression; inflammation; laboratory rat; leukocyte activation /transformation; neuroendocrine system; prolactin; uveitis

In recent years there has been increasing evidence that hormones are capable of regulating the immune system. It has been suggested that prolactin is an immunostimulatory hormone and that reduction of serum prolactin levels in experimental animals by hypophysectomy or treatment with bromocriptine will result in a degree of immunosuppression. An animal model of experimental autoimmune uveitis (EAU) induced by immunization of rats with S-antigen (a soluble antigen from the retina) is used to study intraocular inflammatory disease. We have demonstrated a decrease in antibody production in both male and female rats and a decreased incidence of uveitis in female animals. No significant effect on the immune responses, as measured by lymphocyte proliferation, was seen. As reported before, high doses of cyclosporine (10 mg/kg) result in only partial reduction of intraocular inflammation. We have demonstrated that the suppression of prolactin by concurrent use of bromocriptine in combination with low-dose cyclosporine is more effective than either drug separately in suppressing both the incidence of disease and cellular and humoral immune responses. Evidence in the literature suggests that cyclosporine competes with prolactin for binding sites on lymphocytes. Reductions in prolactin level may reduce competition for those sites and make cyclosporine treatment more effective. Further studies with this animal model will elucidate other aspects of the neuroendocrine axis that may be used to regulate the immune system to treat autoimmune diseases.

近年来，越来越多的证据表明， 能够调节免疫系统。 有人建议 催乳素是一种免疫刺激激素， 通过垂体切除术或治疗的实验动物中的催乳素水平 会导致一定程度的免疫抑制 实验性自身免疫性葡萄膜炎（EAU）动物模型的建立 用S-抗原（来自视网膜的可溶性抗原）免疫大鼠， 用于研究眼内炎性疾病。 我们展示了一个 雄性和雌性大鼠的抗体产生减少， 降低雌性动物的葡萄膜炎发生率。 无显著影响 观察到通过淋巴细胞增殖测量的免疫应答。 如前所述，高剂量环孢菌素（10 mg/kg）仅导致 部分减轻眼内炎症。 我们已经证明 溴隐亭对催乳素抑制作用 与低剂量环孢霉素联合使用比任何一种药物都更有效 分别抑制疾病和细胞的发病率， 体液免疫反应。 文献中的证据表明， 环孢菌素与催乳素竞争淋巴细胞上的结合位点。 催乳素水平的降低可能会减少对这些位点的竞争， 使环孢素治疗更有效。 对此进行进一步研究 动物模型将阐明神经内分泌轴的其他方面， 可用于调节免疫系统以治疗自身免疫性疾病。