Was tumour necrosis factor-alpha responsible for the fetal malformations associated with thalidomide in the early 1960s?

Prescription of thalidomide as a sedative to pregnant women in the early 1960s resulted in a dramatic number of fetal malformations that affected over ten thousand babies. Although tumour necrosis factor-alpha (TNF-alpha) is basically a cytotoxic molecule produced by macrophages when activated by invasive stimuli (such as bacterial endotoxin or tumour growth), it could have an important role in pregnancy, especially in early embryonic development. On these lines, both in human subjects and experimental animals, the cytokine is expressed and synthesized in endometrium, placenta and fetus. Evidence is presented here suggesting that the embryonic action of thalidomide was mediated by TNF-alpha, since the drug is a powerful inhibitor of the synthesis of this cytokine.