Tumour Necrosis Factor in Malignancy

Abstract

TNF is a polypeptide protein composed of subunits of relative moleculer weight of I 7 KD arranged in dimeric, trimeric or pentameric forms depending on the species and isolation method . TNF has two types, TNF-a or cachectin which is produced by activated macrophages , lymphocytes and endothelial cells and TNF-P which is a product of T lymphocytes . TNF protien is encoded by agene stationed on chromosome number 6 . near the M.H.C which is closely linked to the gene for TNF-p. The biological effects ofTNF-a are mediated through the interaction of protein homotrimers with two types of receptors type I ( Pss) and type II ( P1s ). These two receptors are expressed on the cell membrane where they transduce the cytokine signal to the target cell , they can also be identified as circulating soluble proteins generated through proteolytic cleavage of the cell surface receptors . Production of TNF by monocyte I macrophages is regulated by many factors such as L.P.S and dexamethasone which play an important role in regulating TNF production , also cytokines such as GM- CSF, IFN-a·, IL-2 , IL-l and TNF itself can regulate the induction of TNF from monocyte I macrophages . Tumour necrosis factor has been implicated as an important mediator of the lethal effects of endotoxic shock and the cachexia of chronic infection.