Tumor necrosis factor alpha and toxicology

The molecular cloning of a group of proteins, collectively referred to as c ytokines, and including interleukins, chemokines, growth factors, colony st imulating factors, and tumor necrosis factors, has allowed for the increase d understanding of the mechanisms for many disease processes as well as pro vided strategies for the development of novel therapies. Conceptually simil ar to hormones and peptides, this group of phylogenetically related molecul es are also involved in various toxicological processes, including apoptosi s, cell repair, and in particular inflammation. In this review, we offer a description of what many believe represents the primary regulatory cytokine , tumor necrosis factor (TNF)alpha and its role in toxicological processes. For over a decade it has been suspected that this molecule helps mediate t he shock state induced by bacterial endotoxin and the wasting diathesis tha t typifies chronic diseases. Advances in molecular biology that have provid ed tools to modulate TNF alpha regulation and synthesis have allowed for th e identification of additional roles for TNF alpha in homeostasis, cellular damage, and repair. This review provides a brief summary of our understand ing of TNF alpha biology followed by a discussion of its role in toxicologi cal responses. This is followed by specific examples of organ-specific and tissue-specific responses to chemical damage where TNF alpha has been impli cated. The review concludes with a review of its implication in human risk assessment, particularly as it relates to genetic polymorphisms of TNF alph a expression and disease susceptibility.