Tumor Necrosis Factors

Tumor necrosis factors are the cytokines produced mainly by macrophages and T lymphocytes that help regulate the immune response and hematopoiesis (blood cell formation). There are two types of TNF:

TNFa --- also called cachectin, produced by macrophages.
TNFb --- also called lymphotoxin, produced by activated CD4+ T cells.

Human TNFa contains 157 amino acids, generated from a precursor protein of 233 amino acids by a converting enzyme called TACE.  TNFb contains 171 amino acids.  Both TNFa and TNFb bind to the Type I and Type II receptors of the TNF receptor superfamily.  The Type I receptor (TNFRI) has a molecular weight of 55kD while the Type II receptor (TNFRII) has 75kD.  TNFRI contains a death domain which is involved in apoptosis. Most cytokines use the Jak-STAT pathway to transmit signals, but TNF may bind TNFRI to activate the NF-kB pathway.

TNF and IL-1 are structurally unrelated and bind different receptors, but their biological effects are quite similar.  Both can stimulate lymphocyte proliferation and induce acute-phase responses.