Tumor necrosis factor alpha: 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-alpha) secreted by mitogen-stimulated macrophages and lymphotoxin (LT, TNF-beta) 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-alpha 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 alpha (IFN-alpha), interferon gamma (IFN-gamma), and TNF-beta. TNF-alpha also demonstrates both positive and negative cooperative growth-regulatory effects alone and in combination with antitumor drugs as well as with other bioactive peptides. Clinical trials are currently under way to determine the effectiveness of TNF-alpha as a single agent and in combination with biologic and chemotherapeutic agents against a variety of neoplastic diseases in man.
Rosenblum
M G
MG
Department of Clinical Immunology and Biological Therapy, M.D. Anderson Hospital, Houston, Texas.
Donato
N J
NJ
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003001:Cloning, Molecular; D004351:Drug Resistance; D005786:Gene Expression Regulation / Q000187:drug effects; D005796:Genes; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology; D051379:Mice; D009369:Neoplasms / Q000628:therapy; D009857:Oncogenes / Q000187:drug effects; D011487:Protein Conformation; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D012772:Shock, Septic / Q000503:physiopathology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use
D007375:Interleukin-1; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha