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Experimental Biology and Medicine 229:285-290 (2004)
© 2004 Society for Experimental Biology and Medicine

MINIREVIEW

Interferons and Interferon Inhibitory Activity in Disease and Therapy

Kailash C. Chadha*, Julian L. Ambrus, Jr.{dagger}, Wlodzimierz Dembinski{dagger} and Julian L. Ambrus, Sr.{dagger},1

* Department of Molecular & Cellular Biology, Roswell Park Cancer Institute, and {dagger} Department of Internal Medicine, Buffalo General Hospital/Kaleida Health System, State University of New York at Buffalo, Buffalo, New York 14203

To whom requests for reprints should be addressed at 1 Department of Medicine, SUNYAB–Buffalo General Hospital/Kaleida Health System, 100 High St., Rm. E-320, Buffalo, NY 14203. E-mail: jlambrus{at}netscape.net

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}/ß 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.

Key Words: interferon inhibitors • {alpha}/ß type 1 interferon receptors • pathophysiology of neoplastic diseases • viral infections • AIDS • autoimmune diseases




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