Tumor Necrosis Factor-α, Uterine Natural Killer Cells, and Pregnancy.

See related article, pp 1298–1307 Tumor necrosis factor-α (TNF-α) plays a role in any acute or chronic inflammatory disease. The gene was cloned in 1985,1 and the relevance was underscored by 40 years of subsequent research. Indeed, TNF-α inhibition has become a major pastime for many drug companies. Efficacy has been shown most convincingly for inflammatory bowel disease.2 Thus, the proof-of-principle has long since been established. However, moving the anti–TNF-α strategy forward has not been invariably successful. One criticism could be the fact that the approach is too general. Are to be sledgehammers be used when perhaps stilettoes would do? Pregnancy is an immunologic miracle. Thus, the fact that TNF-α plays a role in maladaptive pregnancy, such as gestational hypertension or preeclampsia comes as no surprise; however, the relationships are complex.3 TNF-α and a host of other cytokines join with other molecules, such as soluble fms-like tyrosine kinase-1, endoglin, and the angiotensin II type 1 receptor autoantibody …