TNF and pregnancy: the paradigm of a complex interaction

Although tumour necrosis factor-alpha (TNF) was originally described as a cytotoxic molecule produced by macrophages when activated by certain stimuli (such as bacterial endotoxin or tumour cells), a large body of evidence suggests that TNF plays a role in pregnancy. Both in humans and experimental animals, TNF is expressed and synthesized in the endometrium, placenta and fetus. Here we review evidence in support of positive roles for the cytokine in gestation (such as early pregnancy maintenance, and the contribution of TNF to the maintenance of a complex cytokine-hormone network or to parturition). We also present evidence supporting the idea that TNF acts as a negative regulator of pregnancy, or does not play any significant role in gestation at all.