Interferons and interferon inhibitory activity in disease and therapy.
Interferon (IFN) resistance is an important factor in the pathophysiology of neoplastic disorders, certain viral infections (e.g., AIDS), and autoimmune diseases (e.g., lupus erythematosus and Wegner's granulomatosis). In addition, in some of these disorders, there is also decreased ability to produce IFNs. The capacity of viruses and neoplastic processes to interfere with the IFN system are thought to represent a "virus-against-host" or "cancer-against-host" defense mechanism. Four resistance factors have been identified: 1) release of free IFN-alpha/beta type 1 receptors into the circulation that, at appropriate concentrations, capture and inactivate IFNs; 2) a new IFN inhibitory protein has been isolated and its chemical structure is under study; 3) prostaglandin E2, which is produced by certain tumor cells, inhibits IFN production; and 4) high levels of cAMP phosphodiesterases present, for example in certain tumor cells, reduces cAMP, an important second messenger in IFN synthesis. Studies are under way to reverse these inhibitory effects and to increase endogenous interferon production.
Chadha
Kailash C
KC
Department of Molecular & Cellular Biology, Roswell Park Cancer Institute, State University of New York at Buffalo, Buffalo, New York 14203, USA.
Ambrus
Julian L
JL
Dembinski
Wlodzimierz
W
Ambrus
Julian L
JL
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D001327:Autoimmune Diseases / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D007372:Interferons / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000627:therapeutic use; D009369:Neoplasms / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D017471:Receptors, Interferon / Q000378:metabolism
D017471:Receptors, Interferon; D007372:Interferons