Interferon effects

Merritt, J.A., L.A. Ball, K.M. Sielaff, D.M. Meltzer, and E.C. Borden, Modulation of 2, 5 -oligoadenylate synthetase in patients treated with alpha-interferon effects of dose, schedule, and route of administration. J Interferon Res, 1986. 6(3) 189-98. 

Ehas L, Crissman HA. Interferon effects upon the adenocarcinoma 38 and HL-60 cell lines antiproliferative responses and synergistic interactions with halogenated pyrimidine antimetabolites. Cancer Res 1988 48(17) 4868-73. 

Sidky YA, Borden EC. Inhibition of angiogenesis by interferons Effects on tumor- and lymphocyte-induced vascular responses. Cancer Res 1987 47 5155-5161. 

An interferon-antagonistic substance has been extracted from mouse costal cartilage, and in addition to its anti-interferon effect, it has been shown to share many properties of plant lectins. 2-Amino-2-deoxy-D-glucose and 2-amino-2-deoxy-D-galactose, but not their respective 2-acetamido-deriva-tives, D-glucopyranosyluronic acid and L-rhamnose, are efficient inhibitors of the anti-interferon-induced cell agglutination. 

Interferons (lENs) (52,53), a family of species-specific vertebrate proteins, confer nonspecific resistance to a broad range of viral infections, affect cell proliferation, and modulate immune responses. AH three principal interferons, a-interferon (lEN-a) produced by blood leucocytes, P-interferon (lEN-P) by fibroblasts, and y-interferon (lEN-y) by lymphocytes, also have antiviral activity. The abiUty of interferons to inhibit growth of transplantable and carcinogen-induced tumor led to research showing the direct antiproliferative and indirect immune-mediated antitumor activities (see Chemotherapeutics, anticancer). IENs have been found to be efficacious in certain malignancies and viral infections, eg, hairy cell leukemia (85% response) and basal cell carcinoma (86% response). However, the interferons do have adverse side effects (54). 

Cytokines, eg, interferons, interleukins, tumor necrosis factor (TNF), and certain growth factors, could have antitumor activity directiy, or may modulate cellular mechanisms of antitumor activity (2). Cytokines may be used to influence the proliferation and differentiation of T-ceUs, B-ceUs, macrophage—monocyte, myeloid, or other hematopoietic cells. Alternatively, the induction of interferon release may represent an important approach for synthetic—medicinal chemistry, to search for effective antiinflammatory and antifibrotic agents. Inducers of interferon release may also be useful for lepromatous leprosy and chronic granulomatous disease. The potential cytokine and cytokine-related therapeutic approaches to treatment of disease are summarized in Table 4. A combination of cytokines is a feasible modaUty for treatment of immunologically related diseases however, there are dangers inherent in such an approach, as shown by the induction of lethal disserninated intravascular coagulation in mice adrninistered TNF-a and IFN-y. 

Rhesus monkey kidney infected with Semliki Forest arborvirus gave interferon of tltre 1.5 log interferon units/2 ml. (The interferon unit, determined in a volume of 2 ml, is the dilution of interferon which produced a half-maximal score for degree of cytopathic effect In virus-infected tissue culture tubes at the time when the control without interferon first showed the maximal score.)... 

Agents which enhance the host s response against neoplasias or force them to differentiate are termed biological response modifiers. Examples include interleukin 2 which is used to treat renal cell carcinoma, interferon a which is active against hematologic neoplasias, and tretinoin (all-trans retinoic acid) which is a powerful inducer of differentiation in certain leukemia cells by acting on retinoid receptors. Side effects include influenza like symptoms, changes in blood pressure and edema. 

Cytokines and biological response modifiers represent a broad class of therapeutic agents that modify the hosts response to cancer or cancer therapies. The enormous body information about their clinical uses and their side effects is beyond the scope of this essay that can only give illustrative examples. For an up-to-date information the reader can resort to reference [5]. As many as 33 different interleukins are known and the list continues to grow IL-2 used in the treatment of kidney cancer is one example. Interferon alpha is used for chronic myelogenous leukeia, hairy cell leukaemia and Kaposi s sarcoma. Interferons are also used in the treatment of chronic infections such as viral hepatitis. Tumor necrosis factor (alpha), G/GM/M-CSF, and several other cellular factors are used in treatment of various cancers. Many of these cytokines produce serious side effects that limit their use. 

Common side effects of interferons are flu-like symptoms, fever, myelosuppression, and skin-reactions. 

Interferons (EFNs) are a family of multifunctional secreted proteins in vertebrates. Their most prominent functions are their antiviral properties on homologous cells against a wide range of viruses. It is important to note that prior exposure to EFN is required to render cells resistant to viral infection and replication. In contrast to antibodies, EFNs have no direct neutralizing effect on viruses. 

Chitosan also shows immunopotentiating activity the mechanism involves, at least in part, the production of interferon-gamma and the stimulatory effect on nitric oxide production. Chitosan-based dressings also modulate peroxide production [312,314-318]. 

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