Variations in peripheral blood levels of immunoreactive tumor necrosis factor a (TNFa) throughout the menstrual cycle and secretion of TNFa from the human corpus luteum

Abstract

<h4>Objective</h4>Several cytokines have been implicated as important mediators in the cyclic processes occurring in the reproductive organs. In the present study the peripheral blood concentrations of the cytokines interleukin(IL)-2, IL-6, and tumor necrosis factor (TNF) alpha, as well as the secretion of TNFalpha from the human corpus luteum were investigated.<h4>Study design</h4>The study was undertaken at infertility clinics at large teaching hospitals. Eight women with unexplained infertility undergoing investigations with measurements of endocrine profiles throughout a cycle prior to IVF treatment were included in the study of blood concentrations of cytokines. Blood plasma were taken daily or every second day from a time 3-4 days before expected LH peak until menstruation. The levels of immunoreactive IL-2, IL-6 and TNFalpha were measured by ELISA technique and evaluated (repeated measures ANOVA and Scheffes test) in relation to levels on the day of the LH surge. To investigate a possible ovarian source of TNFalpha, corpus luteum (CL) tissue and cells obtained during the luteal phase from another group of women during abdominal surgery for benign uterine diseases, were cultured for 24 h to assess (ANOVA and Bonferroni test) the release of TNFalpha.<h4>Results</h4>There were no significant fluctuations in the levels of IL-2 and IL-6 throughout the menstrual cycle. The concentration of TNFalpha showed significant fluctuations over the menstrual cycle. Compared to the values on the day of the LH surge, the concentrations were significantly increased during the late follicular phase and during the mid luteal phase. In the early luteal phase the levels were significantly decreased. Measurable levels of TNFalpha were found in the conditioned media from one out of three CL obtained from the early luteal phase, and in all media from CL obtained from mid- and late-luteal phases. Luteal cells in culture secreted TNFalpha, and the levels in the media were not influenced by the presence of hCG (100 IU/L). The conditioned media of luteal cells from late luteal phase contained higher levels than media of cells from early luteal phase, with the levels being higher in media of a mixture of all luteal cells, and large luteal cells as compared to small luteal cells.<h4>Conclusion</h4>This study demonstrates that there are marked fluctuations of blood levels of TNFalpha during the menstrual cycle and that the human CL secretes TNFalpha, with indications of higher secretion during late luteal phase as compared to early luteal phase.