Interleukin-10 attenuates TNF-alpha-induced interleukin-6 production in endometriotic stromal cells.

Objective: To determine whether high levels of interleukin (IL)-10 can attenuate the production of tumor necrosis factor (TNF)-alpha-induced proinflammatory cytokines in endometriotic stromal cells.

Design: Prospective study.

Setting: Department of Ob/Gyn, Tottori University, Japan.

Patient(s): Thirty-five patients with ovarian endometrioma and ten patients with uterine myoma.

Intervention(s): Endometriotic stromal cells were obtained from chocolate cyst linings of ovaries. Endometrial stromal cells obtained from patient with uterine myoma.

Main Outcome Measure(s): Expression of IL-10 gene in endometriotic or endometrial stromal cells was determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). We performed immunohistochemical staining to find the presence of IL-10 and IL-10 receptors 1 and 2. We examined the effects of TNF-alpha and IL-10 on the expression of IL-6 or IL-8 by real-time RT-PCR and ELISA. We examined the activation of intracellular signal transduction molecules in endometriotic stromal cells by Western blotting.

Result(s): Addition of IL-10 suppressed the expressions of IL-6 induced by TNF-alpha and IL-10 induced the phosphorylation of STAT3 in endometriotic stromal cells. TNF-alpha induced the expression of phosphorylated ERK1/2, JNK1/2, and I kappaB. Adding IL-10 suppressed the phosphorylation of these signal molecules.

Conclusion(s): Interleukin-10 attenuates TNF-alpha-induced IL-6 synthesis via NF-kappaB and MAPK pathways in endometriotic cells.. Interleukin-10 may play a significant role in the pathogenesis of endometriosis.