Human tumour necrosis factors-alpha and -beta: differences in their structure, expression and biological properties

Abstract

Tumour necrosis factor-alpha (TNF-alpha) and lymphotoxin (LT or TNF-beta) are cytokines, best known for their cytotoxic or cytostatic effects on some tumour cells. They are structurally related, compete for a common receptor, and are potent inducers of similar biological responses. TNF-alpha and LT appear to have distinct three-dimensional structures because they differ greatly in their sensitivity to various proteases and chemical agents, and antibodies raised against one cytokine do not cross-react with the other cytokine. The closely linked TNF-alpha and LT genes are independently regulated since many cell types produce only TNF-alpha or LT. Expression of the TNF-alpha gene can be controlled either at the transcriptional or at the post-transcriptional level. In some cell types, TNF-alpha and LT induce qualitatively or quantitatively different biological responses, and LT can antagonize the action of TNF-alpha. The disparate biological activities of TNF-alpha and LT may be related to their different interactions with a common receptor. It is possible that TNF-alpha and LT have different physiological roles.