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

Objective: 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 TNF alpha from the human corpus luteum were investigated. Study design: Th e study was undertaken at infertility clinics at large teaching hospitals. Eight women with unexplained infertility undergoing investigations with mea surements of endocrine profiles throughout a cycle prior to IVF treatment w ere included in the study of blood concentrations of cytokines. Blood plasm a 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 TN F alpha were measured by ELISA technique and evaluated (repeated measures A NOVA and Scheffes test) in relation to levels on the day of the LH surge. T o investigate a possible ovarian source of TNF alpha, corpus luteum (CL) ti ssue 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 TNF alpha. Results: There were no significant fluctuations in the levels of IL-2 and IL-6 thro ughout the menstrual cycle. The concentration of TNF alpha showed significa nt fluctuations over the menstrual cycle. Compared to the values on the day of the LH surge, the concentrations were significantly increased during th e late follicular phase and during the mid luteal phase. In the early lutea l phase the levels were significantly decreased. Measurable levels of TNF a lpha 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- an d late-luteal phases. Luteal cells in culture secreted TNF alpha, and the l evels in the media were not influenced by the presence of hCG (100 IU/L). T he conditioned media of luteal cells from late luteal phase contained highe r 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 a s compared to small luteal cells. Conclusion: This study demonstrates that there are marked fluctuations of blood levels of TNF alpha during the menst rual cycle and that the human CL secretes TNF alpha, with indications of hi gher secretion during late luteal phase as compared to early luteal phase. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.