Interferon cell proliferation

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). 

The sterols and sterolins in rice bran are potent immunomodulators. The best response was obtained with a 100 1 sterol/sterolin mixture that demonstrated T-cell proliferation from 20% to 920% and active cell antigens after four weeks in human subjects (Bouic et al, 1996). Another in vitro experimental study with sterol/sterolins, demonstrated a significant increase in cytokinines, interleukin-2 and y-interferon between 17% and 41 % in addition to an increase in natural killer cell activity. These experiments (Bouic et al, 1996) prove that sterol/sterolins are potent immunomodulators with important implications for the treatment of immune dysfunction. Rice bran products are excellent dietary supplements for the improvement of immune function. It is probable that the effects of rice bran on diabetes, CVD and cancer all result from improved immune function. 

Tough, D.F., Borrow, R, and Sprent, J., Induction of bystander T cell proliferation by viruses and type I interferon in vivo, Science, 272, 1947, 1996. 

Asao, H. and Fu, X.Y., Interferon-y has dual potentials in inhibiting or promoting cell proliferation, /. Biol. Chem. 275, S67S74 , 2000. 

Corticosteroids suppress both humoral and cellular immunity. Single doses produce a redistribution of lymphocytes with a concentration dependent decrease of CD4 and CDS positive cells. This in vivo lymphopenic effect correlates with the in vitro inhibition of stimulated T-cell proliferation. Furthermore, corticosteroids are able to inhibit the expression of genes coding for IL-1, IL-2, IL-6, interferon a, and tumor necrosis factor, TNE-a. Chronic administration decreases the size and also the cellu-larity of lymphoid tissues like lymph nodes, spleen, and thymus. Corticosteroids have more effect on the primary immune response and are less effective against previously sensitized immune responses. Their suppressive effects are more pronounced for T-cell immune responses than for the humoral immune response. 

The effects of interferons on the human immune system are highly variable. IFN-p tends to suppress certain aspects of immune function, whereas IFN-a can inhibit immune cell proliferation IFN-y, on the other hand, displays immune-enhancing properties. All three types of interferon have been studied preclinically and even clinically. 

Stimulates T cell expansion and interferon-gamma release the combination of both agents synergistically promotes early hematopoietic cell proliferation... 

As mentioned, interferons also help control abnormal cell proliferation, and these drugs have been approved for use in certain cancers. Interferons are often used as part of the treatment for certain leukemias, lymphomas, and several other forms of cancer (see Table 34-4). Interferon use in cancer chemotherapy is discussed in more detail in Chapter 36. 

The interferons are a family of proteins secreted by animal cells in response to viral and parasitic infections, and are part of the host s defence mechanism. They display multiple activities, affecting the functioning of the immune system, cell proliferation, and cell differentiation, primarily by inducing the synthesis of other proteins. Accordingly, they have potential as antiviral, antiprotozoal, immunomodulatory, and cell growth regulatory agents. 

Ballez JS, Mols J, Burteau CC, Agathos SN, Schneider YJ (2004), Plant protein hydrolysates support CHO-320 cells proliferation and recombinant interferon-gamma production in suspension and inside microcarriers in protein-free media, Cytotechnology 44 103-114. 

Data on bioactivity on immunocompetent cells provide evidence that D-Ala-deltorphin-I potently (10-9 to 10-11 M) and persistently (up to 4 days) enhances Con A-induced mouse spleen cell proliferation [85]. The peptide increases uptake of thymidine and production of interferon--/ in phytohe-magglutinin-activated human lymphocytes [86] and is 100 times more potent than SNC80 in inhibiting the production of p24 antigen, an index of HIV-1 expression, in Jurkat cells stably transfected with a cDNA encoding for the delta-opiate receptor [87]. 

Fantuzzi G, Puren AJ, Harding MW, Livingston DJ, Dinarello CA. Interleukin-18 regulation of interferon gamma production and cell proliferation as shown in interleukin-1 beta-converting enzyme (caspase-l)-deficient mice. Blood 1998 91 2118-2125. 

Other components of the innate response include natural killer (NK) cells and a number of cytokines. NK cells lyse certain types of tumor cells and virally infected cells and are a rich source of immune interferon (interferon-y), which stimulates macrophages and T cells hence they are thought to play an important role in host resistance to both neoplastic and viral disease. Type I interferons (interferon a and interferon P) are produced by a number of different cell types and appear very rapidly after viral infection. Type I interferons inhibit viral replication, inhibit cell proliferation, and increase the lytic potential of NK cells and therefore play a role in controlling viral and neoplastic disease. Several cytokines are important in the initiation of inflammatory responses. Those that have received the most attention include tumor necrosis factor alpha (TNFa), interleukin (IL)-1, and IL-6. There are also a number of chemotactic cytokines (including IL-8), called chemokines, which help to mobilize immune cells to the site of injury. 

Interferon therapy The application of IFN is based on inhibiting protein synthesis and thus cell proliferation. Its indication is recommended in metastatic neuroendocrine tumours. 

Although inhibition of stem-cell proliferation is the most likely mechanism of hematological toxicity, increased platelet hepatic uptake has been suggested to account for thrombocytopenia (227). Raised serum thrombopoietin concentrations were found in patients with interferon alfa-induced thrombocytopenia (228). However, there is evidence that serum thrombopoietin concentrations in patients who have had thrombocytopenia during interferon alfa treatment for chronic viral hepatitis C either do not increase (in patients with compensated cirrhosis) or increase only moderately and less than expected (in non-cirrhotic patients) (229). The authors proposed that interferon alfa impairs liver production of thrombopoietin, raising the possibility of testing thrombopoietin administration in patients with severe thrombocytopenia before or during treatment with interferon alfa (230). 

Kohase, M., Henriksen DeStefiino, D., May, L.T., Vilcek, J. and Sehgal, P.B. (1986). Induction to beta 2-interferon by tumor necrosis fiictor a homeostatic mechanism in the control of cell proliferation. Cell 45, 659-666. 

Interferon-a (IFN-a) Leukocytes B cells proliferation and differentiation NK cells stimulates cytolytic activity Tc cells increases generation APCs increases MHC 1 and II expression Others increases MHC 1 and FcR expression induces antiviral state... 

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