Identity of tumour necrosis factor and the macrophage-secreted factor cachectin

In mammals, several well-defined metabolic changes occur during infection, many of which are attributable to products of the reticuloendothelial system^1-3. Among these changes, a hypertrigly-ceridaemic state is frequently evident^4-9, resulting from defective triglyceride clearance, caused by systemic suppression of the enzyme lipoprotein lipase (LPL)⁹. We have found previously that macrophages secrete the hormone cachectin, which specifically suppresses LPL activity in cultured adipocytes (3T3-L1 cells)^10-17. When originally purified from RAW 264.7 (mouse macrophage) cells, cachectin was shown to have a pI of 4.7, a subunit size of relative molecular mass (M_r) 17,000 and to form non-covalent multimers¹⁷. A receptor for cachectin was identified on non-tumorigenic cultured cells and on normal mouse liver membranes¹⁷. A new high-yield purification technique has enabled us to determine further details of the structure of mouse cachectin. We now report that a high degree of homology exists between the N-terminal sequence of mouse cachectin and the N-terminal sequence recently determined for human tumour necrosis factor (TNF)^18,19. Purified cachectin also possesses potent TNF activity in vitro. These findings suggest that the 'cachectin' and 'TNF' activities of murine macrophage conditioned medium are attributable to a single protein, which modulates the metabolic activities of normal as well as neoplastic cells through interaction with specific high-affinity receptors.