Macrophages against cancer

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Sensitivity to TNF is determined by surface receptors, their study allows to detect tumors, susceptible to exogenous TNF (often they are tumors at a relatively late stage of development), Recently this factor was highlighted in recombinant form of hybrids merge produce TNF cells with E. coli. Consider that the use of tumor necrosis factor for medicinal purposes better be combined with drugs interferon or such chemical agents, as actinomycin, mitomycin C, vinblastine.
A special place among immunomodulators, produced by macrophages and other cells, belongs to interferon, which are now 14 varieties. For the first time this protein has been isolated from the blood cells of virus carrier by the British A. Isaacs and J.. Lindemanns in 1957 He has hampered development in the cells of other viruses and was named by analogy with the phenomenon of interference of viruses (the suppression of one of the virus to others). Interferon is the earliest cell response to infection, it penetrates the cells and interferes with further replication of the virus in threatening or even already begun disease.
Interferon is a product of vital activity of the cell itself, so it has not on the body of unwanted side effects in physiological doses (exception - it pyrogenic effect). Interferon has a distinct species specificity, so the hospital can only be used interferon human origin. Currently, more and more wide application finds recombinant interferon. Adopted by the international unit (ME) of his activity equal of 0.004 ug. The maximum content of the drug in the blood is 2-4 hours after subcutaneous or intramuscular injection (intravenous or oral way less effective), this level is maintained for 6 hours
Interferon has antiviral effect by increasing the synthesis of enzymes that cleave viral particles RNA. Before antibodies to the virus, interferon activates phagocytosis, chemotaxis and bactericidal activity of blood leukocytes. At the same time it stimulates the activity of the EC-cells, macrophages, T-helpers, facilitated the maturation of effector cells. This action of interferon related to increases in lymphoid cells, the expression of antigens tissue compatibility, so say its immunomodulatory activity. The antitumor effect of interferon is connected, apparently, with the strengthening of synthesis of tumor-associated antigens and facilitating their recognition by macrophages and lymphocytes.
There are alpha-interferon (formerly leukocyte),?-interferon (lymphoblastic) and ' -interferon (immune). The largest number of subtypes has alpha-interferon; ascension and?-interferons are virus-induced, and ' - interferon is produced by macrophages and T-lymphocytes during the repeated meeting with the antigen or stimulate their lectins (PHA, Kona). The action of interferon on the immune response depends on its concentration. Low doses stimulate the immune system, large - sometimes alleviate it. The latter is due to the activation of lymphocytes-supressorov also regulated by interferon.
Especially quickly includes suppressor mechanisms exogenous ' -interferon. In model experiments stimulating immunity were dose-human-interferon up to 1000 IU/ml, and concentrations up to 5000 IU/ml inhibited immune function of lymphocytes. Introduction 3 million patients ME intensified cytotoxic activity of killer cells, and the dose of interferon 10 million ME this activity was suppressed.
Macrophages mainly synthesized from-interferon, through which they become dangerous for the tumor cells. But those, in turn, can inhibit the synthesis of interferon production of prostaglandins. One of the means of impeding the production of tumor prostaglandins, is indomethacin.
The impetus for the therapeutic use of interferon was experimental observations of mice that after the introduction of interferon long stanovi were resistant to the virus leukemia. In the clinic interferon alone (liposomes) or in combination with other drugs used for the treatment of osteogenic sarcomas, melanoma, kidney cancer and bowel. Found that interferon helps build killer cells, sometimes causing a halt in the development of tumors (remission), and inhibits the development of metastases. But it is changeable, dose interferon because of the different sensitivities have individually vary (sometimes practicing doses to which sensitive tumour, have to spend on mice-nidah with inoculated tumors person). Important is the creation of a local high concentrations of interferon. Therefore, the best results were obtained in the treatment of interferon leukemia and lymphoma, bladder cancer and ovarian cancer (intraperitoneal administration).
Hopes for an independent anti-tumor effect of recombinant interferon largely failed. It should be noted that more promising is the way of strengthening the production of interferon by the body itself. For this purpose apply various stimulants, including immune RNA. But this stimulation includes complex impact on the entire immune system, and not only on macrophages.