Interleukin-6 differentially stimulates haptoglobin production by peritoneal and endometriotic cells in vitro: A model for endometrial-peritoneal interaction in endometriosis

Based on our previous observation that peritoneal endometriotic (PE) lesion s synthesize in vivo substantially more haptoglobin (Hp) than related eutop ic tissues, we hypothesized that this increase in Hp production was due to endometrial-peritoneal interactions. As interleukin-6 (IL-6) stimulates Hp in other tissues and is produced by endometrial cells, we tested our hypoth esis by evaluating the effects of IL-6 on Hp production by PE cells, normal peritoneal (P) cells, and eutopic endometrial cells from women with (UE-E) and without endometriosis (UE-C) using semiquantitative RT-PCR and enzyme- linked immunoabsorbent assay. Endogenous production of IL-6 was also assess ed. Treatment with human recombinant IL-6 and dexamethasone significantly i ncreased Hp production by P or PE cells in a dose- and time-dependent manne r (P < 0.05). Hp messenger ribonucleic acid was not detected in UE-E and UE -C cells in the absence or presence of IL-6 and dexamethasone. PE and UE-E cells expressed significantly more IL-6 messenger ribonucleic acid than P a nd UE-C cells (P < 0.05). Moreover, UE-E cells secreted 6 times more IL-6 p rotein than UE-C cells (P < 0.05). These findings support our hypothesis an d suggest a novel endometrial-peritoneal interaction whereby locally synthe sized IL-6 and Hp may participate in the establishment and persistence of p eritoneal endometriosis.