Excerpt from Endometriosis Sourcebook

by Sherry Rier, PhD

Although it is not known what factors are responsible for the development and progression of endometriosis, recent studies suggest that endometriosis is associated with immune dysfunction. 1,2 It is known that endometrial tissue is found within the peritoneal cavity of most women; however; only a percentage of women develop endometriosis. Immune cells within the peritoneal cavity may play an important role in the establishment and maintenance of endometriosis. These cells may normally destroy endometrial cells or discourage their growth within the peritoneal environment. Substances produced by cells of the immune system (cytokines) may also participate in endometriosis by influencing the ability of endometrial cells to grow and flourish where they do not belong. In this regard, we have shown that peritoneal leukoytes and endometrial cells from patients with endometriosis aberrantly produce the cytokine interleukin-6 which may result in unregulated growth of endometrial cells. 3,4

Some studies suggest that endometriosis is associated with changes in systemic immunity, that there may be differences in how the immune cells that circulate throughout the body function in women with endometriosis.1 Cytokines are important in regulating the function of immune cells both within the peritoneal cavity and throughout the body. Thus, one approach that scientists have used to study alterations in immunity which accompany different diseases is to study cytokines. If either too much or too little is produced, disease can result. To evaluate how immune cells in the blood in general circulation function in rhesus monkeys both with and without endometriosis, we have examined the ability of these cells to produce interleukin-6 and another cytokine called tumor necrosis factor.5,6 Recently, we have also studied the types of circulating immune cells and their ability to produce several other cytokines (including, interferons, and other interleukins) important in immune function.

In studies funded by the Endometriosis Association, differences were found in the ability of the immune cells to produce interleukin-6 and tumor necrosis factor alpha. Cells from monkeys that had either mild or severe endometriosis could easily be stimulated to produce tumor necrosis factor, while cells from monkeys with no disease could not.

In contrast, animals with disease were able to produce less interleukin-6 than normal monkeys. In fact, less interleukin-6 was produced in severe disease than in those with mild endometriosis. Cells from monkeys with no disease could produce substantially more interleukin-6 than monkeys with disease (either mild or severe).

Interestingly, cytokines are also produced by other cells, including uterine endometrial cells (the cells that are abnormally implanted in the peritoneum of endometriosis patients). It is also known that hormones such as estrogen influence the production of cytokines. A newly emerging idea is that the immune system influences the endocrine (hormonal) system and vice versa - that hormones can influence immunity.

Studies are in progress to further define differences that exist in the immune system of monkeys with endometriosis compared to those that are healthy. It is our hope that continued work will unravel the mystery of how the immune system and endocrine system may function differently in women with endometriosis. This will provide clues to what causes the development of disease and lead to possible prevention or therapy directed at the underlying cause of endometriosis.

Notes

1. J.A. Hill, "Immunologic Factors in Endometriosis - Associated Reproductive Failure, " Infertility and Reproductive Medicine Clinics of North America: Endometriosis 3 (1992): 583-96.

2. W.P. Dmowski, D. Braun, and H. Gebel, "The Immune System in Endometriosis, " Modern Approaches to Endometriosis, E.J. Thomas and J.A. Rock, eds. (Boston: Kluwer Academic, 1992): 97-111.

3. S.E. Rier, A. K. Parsons, and J. L. Becker, "Altered Interleukin-6 Production by Peritoneal Leukocytes from Patients with Endometriosis, " Fertility and Sterility 61 (1994): 294-99.

4.S.E. Rier, P. N. Zarmakoupis, X. Hu, and J. Becker, "Dysregulation of Interleukin-6 Responses in Ectopic Endometrial Stromal Cells: Correlation with Decreased Soluble Receptor Levels in Peritoneal Fluid of Women with Endometriosis, " Journal of Clinical Endocrinology and Metabolism 80 (1995): 1431-37.

5. S.E. Rier, B.L. Spangelo, D.C. Martin, R.E. Bowman, and J. L. Becker, "Production of Interleukin-6 and Tumor Necrosis Factor-Alpha by Peripheral Blood Mononuclear Cells from Rhesus Monkeys with Endometriosis, " Journal of Immunology 150 (1992): 49A.

6. S.E. Rier, D.C. Martin, R.E. Bowman and J.L. Becker, "Immunoresponsiveness in Endometriosis: Implications of Estrogenic Toxicants, " Environmental Health Perspectives 103 (1995).