Tumor necrosis factor-α alters bovine luteal cell synthetic capacity and viability

Tumor necrosis factor-α (TNF-α) is a macrophage-derived cytokine that is also reportedly produced by granulosal cells and is localized in luteal cells. The present study employed serum-free culture of midcycle bovine luteal cells to investigate the effects of TNF-α, alone and with other cytokines, on luteal function. TNF-α (1-1000 ng/ml) produced a dose-dependent increase in prostaglandin (PG)F_2α and 6-keto-PGF1α synthesis on all days of culture, but had no effect on basal progesterone (P₄) production. TNF-α, in combination with other known stimulators of luteal PG synthesis, interleukin-1β (2.5 ng/ml) or interferon-γ (IFN-γ, 100 U/ml), had synergistic effects on PGF_2aα production (>50-fold above control, P < 0.05) whereas interferon-α (1000 U/ml) significantly suppressed TNF-α-stimulated PGF_2α production. By day 7 of culture, TNF-α inhibited LH-stimulated P₄ production (P < 0.05). Luteal cell numbers were significantly reduced by IFN-γ but not by TNF-α alone. However, the combination of TNF-α + IFN-γ was extremely cytotoxic (only 20% of cells maintained as compared to control). Finally, TNF-α (100 ng/ml) enhanced the expression of Class I major histocompatibility complex antigens on cultured bovine luteal cells but did not alter IFN-γ induction of Class II major histocompatibility complex antigens. In light of these findings, it appears that TNF-α, in conjunction with other cytokines, is a modulator of luteal cell function in vitro. The stimulation of PG synthesis, as well as cytotoxic effects of TNF-α, may suggest a role in luteolysis.