Expression of allograft inflammatory factor-1 in human eutopic endometrium and endometriosis: possible association with progression of endometriosis.

Allograft inflammatory factor-1 (AIF-1) is a cytokine originally identified in rat cardiac allografts with chronic rejection. AIF-1 is expressed in various human immune-related tissues and is thought to play a role in inflammatory responses and the immune activation and function of macrophages. Expression has also been shown in human placentas and bovine embryos, suggesting that AIF-1 may be involved in reproductive function. Immune factors are thought to be involved in the pathogenesis of endometriosis. High concentrations of activated macrophages and various cytokines have been found in the peritoneal fluid of patients with endometriosis. In the current work we examined the expression of AIF-1 in human eutopic endometrium and endometriosis, and measured AIF-1 in peritoneal fluid samples from women with and without endometriosis. RT-PCR, Western blot analysis, and immunohistochemistry showed that AIF-1 mRNA and protein were expressed both in eutopic endometrium and in endometriotic tissue. In eutopic endometrium, expression was greater in the late secretory and menstrual phases than in other phases of the menstrual cycle (P < 0.01). AIF-1 protein was present in greater amounts in peritoneal fluid from patients with endometriosis than in women without it (P < 0.01), and its concentration correlated with the Revised American Society for Reproductive Medicine score (rs = 0.693; P < 0.0001). Peritoneal macrophages from endometriosis patients secreted more AIF-1 than those from unaffected women (P < 0.05). AIF-1 release from macrophages was stimulated by IL-1beta (P < 0.01) and interferon-gamma (P < 0.05). These results demonstrate for the first time that AIF-1 is expressed in eutopic endometrium and endometriotic tissue, suggesting that AIF-1 is one cytokine in the local network involved in the onset of menstruation. AIF-1 derived from peritoneal macrophages may also possibly play a significant role in the pathophysiology and progression of endometriosis.