The possible anti-inflammatory role of circulating human leukocyte antigenlevels in women with endometriosis after treatment with danazol and leuprorelin acetate depot

BACKGROUND: Endometriosis is defined as an inflammatory condition of the fe male reproductive tract, a state often associated with infertility and misc arriage. Many exogenously administered factors (treatments) control the dis ease via as yet unknown pathways. Possible candidate molecules involved in these mechanisms could be the serum-soluble human leukocyte antigens (sHLA) that have been detected in a variety of human body fluids and that are ass ociated with several diseases. Aims: We here examine how danazol and leuprorelin acetate depot treatments exert their anti-inflammatory action. It is plausible that subtle alteratio ns mediated by these treatments and in relation to sHLA may explain the pat hophysiology of endometriosis and provide insights towards new therapeutic protocols. Methods: Indirect enzyme-linked immunosorbent assay (ELISA), using specific monoclonal antibodies, determined serum-soluble class-I and class-II HLA l evels. ELISA readings from treated women were compared with normal healthy subjects. Results: Serum-soluble class-I and class-II HLA levels are statistically si gnificantly lower (P < 0.001) in women with endometriosis than in the contr ol groups. However, danazol but not leuprorelin acetate depot administratio n augments soluble HLA class I and class II (P < 0.01 and P < 0.001, respec tively) to normal levels during the treatment period, an increase that may account for the anti-inflammatory effect and the remission observed. Conlusions: 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. Da nazol administration acts via an induced release of these antigens, whose p resence correlates with the degree of the inflammatory alleviation obtained . We thus provide evidence that the inflammatory state of the disease appea rs to be associated with soluble HLA levels because, 3 months after ceasing therapy, the circulating antigens in the serum return to the same levels t hat correspond to the pathological condition.