Cytokines antiviral effects

The enhanced production of the cytokines called interferons is one of the body s earliest responses to a viral infection. These endogenous proteins exert potent antiviral, immunoregulatory, and antiproliferative effects and are classified according to the cell type from which they were initially derived. Interferon-a (type I, leukocyte) and interferon (3-(3 (type I, fibroblast) are synthesized by most types of cells in response to viral infection, certain cytokines, and double-stranded RNA. Interferon-y (type II, immune) is produced by natural killer (NK) cells and T lymphocytes in response to antigens, mitogens, and certain cytokines. Interferon-a and interferon-(3 exert the most potent antiviral effects interferon-y is antiviral and strongly immunomodulatory. 

Mechanism of Action. Although the details are unclear, imiquimod enhances the local production of interferons, tumour necrosis factor-alpha, and possibly other cytokines that produce antiviral responses. Hence, this drug does not act directly on the virus, but instead modulates the host (human) immune responses that have antiviral effects. 

The individual response of cells to TNF binding includes induction of proliferation, differentiation, cell survival, or cell death (Wallach 1997). Several lines of evidence suggest that TNF exerts an antiviral effect. At high concentrations TNF can inhibit the replication of certain viruses (including Ads) in vitro, possibly by inducing lysis and/or apoptosis of infected cells. However, as TNF-mediated activation of NF-kB induces a variety of inflammatory cytokines, TNF may also exert its antiviral function indirectly (Hatada et al. 2000). Cytolysis by TNF appears to involve CPLA2, which is activated by MAP kinase and possibly caspase-8 (Wissing et al. 1997 Wallach et al. 1999) and is translocated to membranes where it can release arachidonic acid (AA). 

IFN-a production, while IL-18 production was not increased. Moreover, EPS-1, at a concentration of 100 microg/mL, induced the production of IL-12 at considerable levels IFN-y and TNF-a were also detected. The immunomodulatory activity of EPS was correlated to evaluation of its antiviral effect [55]. A similar study was published later in a paper by Arena et at, in which the immunomodulatory and antiviral effects of an exopolysaccharide EPS-2, isolated from a strain of Geobacillus thermodendrifi-cans, were described. EPS-2 also stimulated the cytokine production in PBMC cells in a concentration-dependent manner, like EPS-1. A high level of IL-12, IFN-y, TNF-a and IL-18 was revealed after EPS-2 treatment [56]. 

Anthelmintic, antiprotozoal, anti-neoplastic, and antiviral agent Binds many proteins, i.e., cytokines. epidermal growth factor, and members of the FGF family inhibits dengue virus infec-tivity of host cells very long in vivo half-life, exhibits a wide range of toxic side effects 40-47... 

Comments on the generally favorable effects of lithium on immune function have been summarized (46). The antiviral and neuroprotective properties of lithium were mentioned in a review of the immune system and bipolar disorder (47). The potential benefit of lithium in treating AIDS and AIDS-related dementia, owing in part to its cytokine-regulating and neuroprotective effects, has been reviewed (48). Genital Herpes simplex infection has responded to lithium (49). 

Interferons, which were discovered in the 1950s as a result of their antiviral activity (76), are pleiotropic agents exhibiting a wide variety of effects including antiviral, antiproliferative, hematopoietic, and immunomodulatory activities (77, 78). Interferons are sometimes considered to be cytokines because of their role in cellular and humoral immune responses. 

Interferons (IFN), cytokines that display antiproliferative, antitumor, antiviral, and immunomodulatory properties. They regulate somatic cell growth, division, and apoptosis. The biological effects of IFNs are primarily mediated via activation of the JAK/STAT pathway. IFN are glycoproteins secreted by virus-infected vertebrate cells preventing viral proliferation, largely by inhibition of protein synthesis in other infected cells. Three families of IFN have been characterized (a) IFN-a or leukocyte... 

Mackewicz CE, Ortega H, Levy JA. Effect of cytokines on HTV replication in CD4-I- lymphocytes lack of identity with the CD8+ cell antiviral factor. Cell Immunol 1994 153 329-343. 

Johnson PA, MacLean C, Marsden HS, Dalziel RG, Everett RD (1986) The product of gene USll of herpes simplex virus type 1 is expressed as a true late gene. J Gen Virol 67 871 883 Kerr IM, Brown RE (1978) pppA2 p5 A2 p5 A an inhibitor of protein synthesis synthesized with an enzyme fraction from interferon-treated cells. Proc Natl Acad Sci USA 75 256 260 Khabar KS, Dhalla M, Siddiqui Y, Zhou A, Al-Ahdal MN, Der SD, Silverman RH. Williams BR (2000) Effect of deficiency of the double-stranded RNA-dependent protein kinase, PKR, on antiviral resistance in the presence or absence of ribonuclease L HSV-1 replication is particularly sensitive to deficiency of the major IFN-mediated enzymes [In Process Citation]. J Interferon Cytokine Res 20 653-659... 

Signal transducers and activators of transcription, STATs a family of DNA-binding proteins. Biological effects of STATs range from antiviral responses to cell transformation, and they appear to be particularly involved in signaling pathways activated by cytokines So far, 6 STATs and their corresponding genes have been identified in mammals, and 2 in Drosophila. 

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