Matalliotakis I M, Athanassakis I, Goumenou A G, Neonaki M A, Koumantakis E E, Vassiliadis S, Koumantakis E E
Department of Obstetrics and Gynecology, University Hospital, University of Crete, Heraklion, Greece.
Mediators Inflamm. 2001 Apr;10(2):75-80. doi: 10.1080/09629350120054545.
Endometriosis is defined as an inflammatory condition of the female reproductive tract, a state often associated with infertility and miscarriage. Many exogenously administered factors (treatments) control the disease via as yet unknown pathways. Possible candidate molecules involved in these mechanisms could be the serum-soluble human leukocyte antigens (sHIA) that have been detected in a variety of human body fluids and that are associated with several diseases.
We here examine how danazol and leuprorelin acetate depot treatments exert their anti-inflammatory action. It is plausible that subtle alterations mediated by these treatments and in relation to sHLA may explain the pathophysiology of endometriosis and provide insights towards new therapeutic protocols.
Indirect enzyme-linked immunosorbent assay (ELISA), using specific monoclonal antibodies, determined serum-soluble class-I and class-II HLA levels. ELISA readings from treated women were compared with normal healthy subjects.
Serum-soluble class-I and class-II HLA levels are statistically significantly lower (P < 0.001) in women with endometriosis than in the control groups. However, danazol but not leuprorelin acetate depot administration augments soluble HLA class I and class II (P < 0.01 and P < 0.001, respectively) to normal levels during the treatment period, an increase that may account for the anti-inflammatory effect and the remission observed.
It is shown that one of the underlying causes of endometriosis may be the lack of both circulating class-I and class-II antigen levels. Danazol administration acts via an induced release of these antigens, whose presence correlates with the degree of the inflammatory alleviation obtained. We thus provide evidence that the inflammatory state of the disease appears to be associated with soluble HLA levels because, 3 months after ceasing therapy, the circulating antigens in the serum return to the same levels that correspond to the pathological condition.
子宫内膜异位症被定义为女性生殖道的一种炎症性疾病,这种状态常与不孕和流产相关。许多外源性给予的因素(治疗方法)通过尚不清楚的途径控制该疾病。参与这些机制的可能候选分子可能是血清可溶性人类白细胞抗原(sHLA),其已在多种人体体液中被检测到,且与多种疾病相关。
我们在此研究达那唑和醋酸亮丙瑞林缓释剂治疗如何发挥其抗炎作用。由这些治疗介导的与sHLA相关的细微改变可能解释子宫内膜异位症的病理生理学,并为新的治疗方案提供见解,这是合理的。
使用特异性单克隆抗体的间接酶联免疫吸附测定(ELISA)法测定血清可溶性I类和II类HLA水平。将接受治疗的女性的ELISA读数与正常健康受试者进行比较。
子宫内膜异位症女性的血清可溶性I类和II类HLA水平在统计学上显著低于对照组(P < 0.001)。然而,在治疗期间,达那唑而非醋酸亮丙瑞林缓释剂给药可使可溶性I类和II类HLA增加至正常水平(分别为P < 0.01和P < 0.001),这种增加可能解释了观察到的抗炎作用和缓解情况。
结果表明,子宫内膜异位症的潜在病因之一可能是循环I类和II类抗原水平均缺乏。达那唑给药通过诱导这些抗原的释放发挥作用,这些抗原的存在与所获得的炎症缓解程度相关。因此,我们提供证据表明该疾病的炎症状态似乎与可溶性HLA水平相关,因为在停止治疗3个月后,血清中的循环抗原恢复到与病理状态相对应的相同水平。