Biochemical characterization and metabolic effects of tumor necrosis factor.

Abstract

The tumor necrosis factor, preliminary identified because of its antitumor properties, refers to two kinds of similar polypeptides (TNF or cachectin, and TNF-beta or lymphotoxin), which share some biological effects. Both substances, as members of the class of cytokines, play a role as mediators of inflammation and the cellular immune response. Human cachectin is produced as a prohormone and activated by cleavage of a 76 residue peptide. Mature cachectin (which comprises 157 amino acid residues) share a 28% amino acid sequence homology with lymphotoxin. Both cytokines are encoded by different genes of chromosome 6 and may compete for a common receptor. Cachectin is produced by a wide variety of cells (phagocytic and non-phagocytic), mainly by activated macrophages and monocytes. Different invasive stimuli (mainly lipopolysaccharide, a constituent of the Gram-negative bacteria's outer wall) activate cachectin biosynthesis, which is controlled chiefly at a post-transcriptional level. The newly synthetized cachectin remains associated as a transmembrane form, affecting their targets by direct cell-to-cell contact, or is actively secreted in the circulation to distant sites in the body, where it binds to high affinity cachectin receptor, on a variety of cell types. Cachectin exerts pleiotropic effects on normal, transformed, or tumoral cells. The biological effects mediate by cachectin may be beneficial or deleterious to the body, depending on the quantity produced, duration of cell exposure and further biochemical mediators in the environment of the target cells. Cachectin (frequently associated with severe infection and cancer) seems to be the result of a persistent exposure to raised levels of cachectin.(ABSTRACT TRUNCATED AT 250 WORDS)