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Interleukin-1 (IL-1) Regulation of Human Endometrial Function: Presence of IL-1 Receptor Correlates with IL-1-Stimulated Prostaglandin E₂ Production^*

Department of Pathology, City Hospital Center (S.T.) Elmhurst, New York 11373
Mount Sinai School of Medicine (S.T.) New York, New York 10029
Hoffmann-La Roche, Inc. (K.L.K., P.L.K.) Nutley, New Jersey 07110
The Department of Obstetrics and Gynecology, Milton S. Hershey Medical Center, Pennsylvania State University (P.G.S.) Hershey, Pennsylvania 17033

Address all correspondence and requests for reprints to: S. Tabibzadeh, M.D., Department of Pathology, City Hospital Center, Elmhurst, New York 11373.

Previous studies suggest that prostaglandin E₂ (PGE₂) is important in normal endometrial function and that it may be involved in certain uterine dysfunctions. In this study, the ability of the purified E. coli-derived recombinant interleu-kin-l (rIL-1) to regulate the production of PGE2 by the endometrial epithelium is investigated. PGE₂ levels determined by the RIA consistently increase upon incubation of cultured glandular epithelial cells with rIL-1. A significant increase is obtained with 17 and 170 ng/L rIL-1. A maximal effect is obtained within 24 h of incubation with rIL-1. In the seven endometria evaluated, rIL-1 increases PGE₂ synthesis in all cases, but the maximal increase relative to the basal levels varies between 2- to 10-fold for a given preparation. Vibratome sections retaining the integrity of the endometrial tissue also show an increased PGE₂ synthesis in response to rlL-1. rlL-1-stimulated PGE₂ production is blocked by the addition of a neutralizing antibody to rIL-1. In addition, indomethacin, a cycloox-ygenase inhibitor, suppresses both rIL-1-induced and basal PGE₂synthesis. Experiments using radioiodinated rIL-1 reveal that the membranes prepared from human endometrial epithe-lium possess high affinity receptors for IL-1, suggesting that IL-1 regulates PGE2 synthesis by binding to this receptor site. The expression of IL-1 receptors and the ability to modulate PGE₂ production by IL-1 in endometrial epithelium suggest that IL-1 may play a significant role in human uterine function via modulation of PGE₂ production.

^* This work was supported in part by USPHS Research Grants CA-6866-01A1 (to S.S.T.) and CA-46349 (to P.G.S.).

Received September 15, 1989.

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