Tumor necrosis factor α: A multifaceted peptide hormone

Homeostasis at the cellular level appears to be a complex state of equilibrium derived, in part, from multiple interactions among lymphokines, cytokines, growth factors, and hormones. Tumor necrosis factor (TNF-α) secreted by mitogen-stimulated macrophages and lymphotoxin (LT, TNF-β) produced by mitogen-stimulated lymphocytes are two peptide hormones that share considerable homology in amino acid sequence and biological action. It has become increasingly evident that these factors, primarily involved in host defense, also mediate some responses to inflammatory, infectious, and neoplastic disease states. TNF-α is a low molecular weight (17,000-kdalton) peptide which seems to have a remarkably broad range of biological and immunologic effects, including antiviral action, growth regulation, and immunomodulation. These effects are shared by other lymphokines and cytokines such as interleukin 1 (IL-1), interferon α (IFN-α), interferon γ (IFN-γ), and TNF-β. TNF-α also demonstrates both positive and negative cooperative growth-regulatory effects alone and in combination with antitumor drugs as well as other bioactive peptides. Clinical trials are currently under way to determine the effectiveness of TNF-α as a single agent and in combination with biologic and chemotherapeutic agents against a variety of neoplastic diseases in man.