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Inhibitory effect of interferon and tumor necrosis factor on human luteal function in vitro
Insights
Immunological mechanisms, specifically interferon-gamma (IFN-gamma), inhibit progesterone production in human luteal cells. This suggests a role for cytokines in luteal function and regression.
Area of Science:
- Reproductive immunology
- Endocrinology
- Cell biology
Background:
- Human luteal function is crucial for reproduction.
- The role of immunological factors in luteal function is not fully understood.
Purpose of the Study:
- To investigate the involvement of immunological mechanisms in human luteal function.
- To examine the effects of cytokines on steroidogenesis in human luteal cells.
Main Methods:
- Human luteal cells from 17 women were cultured in vitro.
- Cells were treated with interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha).
- Steroid production (progesterone and estradiol) was measured after 48 and 96 hours.
Main Results:
- IFN-gamma dose-dependently inhibited basal and hCG-stimulated progesterone production.
- Progesterone production was reduced by approximately 45% at 48 hours and further at 96 hours.
- IFN-gamma's inhibitory effect was neutralized by a monoclonal antibody, suggesting endogenous IFN-gamma has a tonic inhibitory role.
Conclusions:
- IFN-gamma and TNF-alpha can inhibit progesterone production in human luteal cells.
- These cytokines, known for antiviral functions, may also regulate luteal function and contribute to luteal regression.
Objective:
To investigate whether immunological mechanisms may be involved in human luteal function.
Design:
The effects of the cytokines, interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) on steroidogenesis by human luteal cells were examined in vitro. The dispersed human luteal cells, obtained from a total of 17 women at laparotomy, were cultured separately in the presence or absence of human chorionic gonadotropin (hCG) and IFNs/TNF-alpha with the medium being replaced at 48 hours. The medium was collected at 48 and 96 hours for steroid assays.
Results:
The IFN-alpha had no significant effect on the production of estradiol or progesterone (P), whereas a dose-related inhibition of basal, as well as hCG-stimulated P formation, was observed after the addition of IFN-gamma (10 to 1,000 U/mL). Progesterone production was inhibited to about 45% of the control at 48 hours and even lower at 96 hours (n = 6, P < 0.001). The combination of IFN-gamma and low doses of TNF-alpha induced a further significant inhibition, whereas there was no effect of TNF-alpha alone. This inhibitory effect of IFN-gamma could be completely neutralized with a monoclonal antibody to IFN-gamma. Incubation with the antibody alone increased the production of P from luteal cells in culture, suggesting a local tonic inhibitory action of endogenous IFN-gamma.
Conclusion:
Interferon-gamma and TNF-alpha, whose function classically is known as antiviral, also may play a role in human luteal regression by inhibiting luteal P production.