Tumor necrosis factor/TNF alpha [TNFA/1172]

Tumor necrosis factor alpha (TNF-alpha) is a protein secreted by lipopolysaccharide-stimulated macrophages, and causes tumor necrosis when injected into tumor bearing mice. TNF-alpha is believed to mediate pathogenic shock and tissue injury associated with endotoxemia. TNFalpha exists as a multimer of two, three, or five non-covalently linked units, but shows a single 17kDa band following SDS-PAGE under non-reducing conditions. TNF-alpha is closely related to the 25kDa protein tumor necrosis factor beta (lymphotoxin), sharing the same receptors and cellular actions. TNF-alpha causes cytolysis of certain transformed cells, being synergistic with interferon gamma in its cytotoxicity. Although it has little effect on many cultured normal human cells, TNF-alpha appears to be directly toxic to vascular endothelial cells. Other actions of TNFalpha include stimulating growth of human fibroblasts and other cell lines, activating polymorphonuclear neutrophils and osteoclasts, and induction of interleukin 1, prostaglandin E2, and collagenase production. TNF-alpha is currently being evaluated in the treatment of certain cancers and AIDS related complex.