Interferon production effect

Blakley BR, Archer DL, Osborne L. 1982. The effect of lead on immune and viral interferon production. Can J Comp Med 46 43-46. 

In addition to directly eliciting cell chemotaxis and free-radical production, PAF can also induce the release of various inflammatory cytokines, amongst which tumour necrosis factor (TNF) is of particular importance [ 312 ]. We have recently shown that PAF stimulates TNF production from peripheral blood derived monocytes and at picomolar concentrations amplifies lipopoly-saccharide (LPS)-induced TNF production, effects inhibited by various PAF antagonists [313]. PAF also acts synergistically with interferon-y (IFN-y) to increase the monocyte cytotoxicity. Furthermore, PAF can modulate the production of both interleukin 1 and interleukin 2 (IL-1, IL-2) from rat monocytes and lymphocytes, respectively [222, 223], cytokines which in turn elicit the release of other mediators and growth factors. 

NTl 64 Sonnenfeld, G. Effect of sidestream tobacco smoke components on alpha/ beta interferon production. Oncology 1983 40(1) 52-56. 

The formation and release of interferon by viral and other pathological stimulation has resulted in a search for chemical inducers of endogenous interferon. Administration of a wide range of compounds has resulted in induction of interferon production. However, no clinically useful compounds have been found for humans, although tilorone is effective in inducing interferon in mice. 

Baker PN, Morser J Burke DC (1980) Effects of sodium butyrate on a human lymphoblastoid cell line (Namalwa) and its interferon production. Journal of Interferon Research 1 (1) 71-77. 

The biological activity of polycarboxylates, polynucleotides and small molecular weight interferon inducers (e.g tilorone) is not restricted to interferon production. In vivo, they exert many other effects on host defense mechanisms, including an increase of the body temperature (pyrogenicity), a stimulation of humoral and cellular immune responses (immuno-adjuvant effect), and an enhancement of the reticulo-endothelial cell activity (phagocytosis) (Fig. 8). 

In vivo, interferon inducers exert a wide variety of effects on host defense mechanisms interferon production, pyrogenicity, stimulation of cellular and humoral immunity and stimulation of reticulo-endothelial activity. It is not surprising, therefore, that interferon inducers increase the host s resistance to both viral and non-viral (bacterial, fungal, protozoal) infections and tumor growth. A major obstacle confronting the clinical usefulness of interferon inducers is their toxicity. Are interferon induction and toxicity necessarily coupled or can they be disconnected Preliminary evidence suggests that, at least with poly(I) poly(C), toxicity and activity could be uncoupled. 

Sonnenfeld G, Hudgens RW, Streips UN. 1983. Effect of environmental carcinogens and other chemicals on murine alpha-beta interferon production. Environ Res 31 355-361. 

Blanchard DK, Newton C, Klein TW, Stewart WE, Friedman H (1986) In vitro and in vivo suppressive effects of delta-9-tetrahydrocannabinol on interferon production by murine spleen cells. Int J Immunopharmacol 8 819-824... 

Thymosins. Thymosins are hormone-like polypeptides produced by thymus epithelial cells. They regulate the maturation of T-cells moreover, they modulate interferon production and stimulate the expression of interleukin-2 and its receptor. A trial of thymosin fraction-5 in four homosexual patients with chronic hepatitis B demonstrated no effect after six months of treatment (202), while treatment of WHV-infected woodchucks with thymosin alpha-1 resulted in clearance of circulating WHV-DNA and a 50-300-fold decline in the levels of replicative intermediates in liver tissue (203). Subsequently, thymosin alpha-1 and thymosin fraction-5 were used to treat chronic hepatitis B in a human pilot study (204). Results were encouraging, and this was followed by several randomized, controlled multicenter trials of thymosin alpha-1 in the U.S. The primary action of thymosin is unknown, but it is probably related to its immune-enhancing effects. 

Actions Antioxidant, anti diuretic, smooth muscle relaxant, antispasmodic, immunostimulant (stimulates interferon production, enhances antibody formation, stimulates phagocytosis, antistressor, adrenal tonic, thymus stimulant), antiulcer, anti-inflammatory, tumor inhibitor, free radical inhibitor, antihepatoxic, antimalarial, protects from effects of radiation exposure, gentle laxative, expectorant, demulcent, immunomodulator, antihyperglycemic, reduces gastric secretions, stimulates pancreatic secretions. 

Other double-stranded molecules have been examined and found to show inducing and toxic effects [119], The polyadenylic-polyuridylic acid complex (poly A U) is a much weaker inducer, and less toxic, than poly I C but it is much less thermally stable and more readily degraded by enzymes. Substitution of the phosphate groups by thiophosphate gave a more stable complex and increased its ability to stimulate interferon production [120]. 

Ascorbate has also been shown to enhance interferon production (92, 298-301), as well as to enhance the phagocytic properties of the reticuloendothelial system, both potent in vivo defenses against viruses. The interaction of ascorbate with L-lysine in rats (67) may also contribute to the effectiveness of ascorbate. 

The ability to hydrolyze poly I poly C is much greater in human serum than in mouse serum. In general, animal species that have high hydrolytic capacity are poor responders to poly I poly C, and go.od responders have low hydrolytic capacity. While these observations are consistent with the idea that there is a cause and effect relationship between hydrolytic capacity and interferon production, they certainly do not establish such a cause and effect relationship. One of the points that will be emphasized in this review deals with the frequency with which hydrolysis resistance of a polynucleotide is associated with its ability to induce interferon in primates. 

Hilleman and his co-workers have demonstrated interferon production following the administration of reovirus RNA or the replicative form of RNA isolated from E. coli infected with MS2 coliphage. These BNAs are effective in inducing resistance to virus infection m vitro and vivo. The induction of interferon and the broad-spectrum protection against viral infection conferred by double-stranded RNA suggested the use of synthetic polynucleotides, including polyriboinosinic-polyribocytidilic acid, which possess a double-stranded conformation. Chemically modified RNA may also induce the production of interferon. ... 

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