Tumour necrosis factor α (TNF α ) is a pro‐inflammatory cytokine that plays a key role in the pathogenesis of many infections and inflammatory diseases. 1 It was identified through its ability to lyse tumour cells,2 but in retrospect this ability was first noted nearly 100 years ago, when Coley's toxins were shown to destroy sarcoma cells. TNF α is now recognized to be involved in stimulation of cytokine production, enhancing expression of adhesion molecules and neutrophil activation, and it is also a co‐stimulator for T‐cell activation and antibody production by B cells. 1 As such, it contributes to the regulation of normal homeostasis, as well as playing an important role in inflammation. TNF α belongs to a family of proteins that includes lymphotoxin α (LT α , previously known as TNF β ) and lymphotoxin β (LT β ). Although T cells can produce TNF α , activated monocytes (macrophages) are the major source of TNF α , which is synthesized as a 20 kDa pro‐protein and cleaved by TNF α converting enzyme (TACE) to a 17 kDa monomer. Under physiological conditions, TNF α circulates as a stable cone‐shaped homotrimer3 that mediates its effects by binding to two receptor molecules TNF RI (p55) and TNF RII (p75).1 Genes for these receptors also contain polymorphic variants, but these are beyond the scope of this review. By the mid 1980s, the TNF α protein had been purified, and its gene cloned, sequenced and mapped to the MHC Class III region on the short arm of chromosome six.4 The TNF α gene is tandemly arranged with that for LT α and LT β , within the ‘TNF locus’, a 7 kb region 250 kb centromeric to the HLA B locus, 400 kb telomeric to the C2/BF locus and ∼1000 kb from the MHC Class II DR genes …