This study aims to assess the specific toxicity (allergenicity, immunotoxicity and reproduction toxicity) of a dosage form of complement C3 neodeterminant recombinant humanized antibody. The reactions of general anaphylaxis, active cutaneous anaphylaxis and delayed-type reaction demonstrated no drug-related signs of experimental animal sensitization and immediate or delayed hypersensitivity in the treated animals. It was found that, in doses exceeding significantly the expected human therapeutic dose, the drug has no effect on humoral and cell-mediated immune responses. In addition, the drug does not suppress the phagocytic cell activity thereby indicating the absence of immunotoxic effect. Moreover, the drug has no adverse effects on male and female reproduction, progeny embryonal development, as well as prenatal and postnatal progeny development. The obtained data can be used in future clinical studies of the drug safety.

A drug based on complement C3 neodeterminant recombinant humanized antibody for the treatment of traumatic brain injuries belongs to the class III of low-risk drugs.

В настоящей работе исследована противоопухолевая активность активированного рекомбинантного антимюллерова гормона (рАМГ) человека в отношении клеток линий NBL-7 и OVCAR3. Показано, что гормон, содержащийся в высокоочищенных препаратах, обладает не только способностью к связыванию c рекомбинантным рецептором II типа (MISRII), но и цитотоксическим эффектом в отношении клеток, экспрессирующих MISRII. Полученные данные могут лечь в основу разработки первого отечественного противоопухолевого лекарственного средства на основе активированного рАМГ.

In the present study, the antitumor activity of activated recombinant human anti-Mullerian hormone (rAMH) against the NBL-7 and OVCAR3 cell lines was investigated. It was shown that the hormone contained in highly purified preparations not only has the ability to bind to the recombinant type II receptor (MISRII), but also possesses a cytotoxic effect against cells expressing MISRII. The obtained data may underlie the basis for the development of the first domestic anticancer drug based on activated rAMH.

The paper deals with the effect of glutoxim included into a preoperative preparation regimen on immunological parameters in patients with fibrocavernous pulmonary tuberculosis. On admission, all the patients had inadequate cellular immunity and activated humoral immunity. After termination of a course of glutoxim therapy, there was an increase in the baseline low values of lymphocytic proliferative activity, in the count of mature T lymphocytes, and in the production of IL-2 induced by phytohemagglutinin. At the same time the similar parameters remained unchanged in the control group. The drug exerted the most noticeable stimulating effect on cellular immunity in patients with a limited process. Glutoxim produced no noticeable effect on humoral immunity. The immunomodulating effect of glutoxim was followed by improvement of the clinical and X-ray pictures of the disease. In glutoxim-treated patients with baseline immunological disorders, progression was found to occur 1.5-2 times more infrequently than in the control group. Indications for the use of glutoxim in the treatment of tuberculosis are specified on the basis of the baseline immunological parameters of each patient.

The serum activity of the enzyme adenosine desaminase (ADA) was studied in patients with infiltrative tuberculosis in relation to IL-1 beta, TNF-alpha, IL-2 productions, the magnitude of a lymphocytic proliferative response to PPD and PGA. There was an association of high ADA levels with the severity of a tuberculous process, with the least IL-2 production together with drastically increased IL1 beta and significant disorders in the TNF-alpha system. Moderate ADA increases reflect the regularly enhanced activity of immunocompetent cells in response to an infectious agent. The findings indicate that a simple biochemical test may be used for rapid preliminary evaluation of the severity of disease and immune performance.

The specific features of production of IL-1 beta, TNF-alpha, IL-2 were studied in 74 patients with various forms of tuberculosis by taking into account the magnitude of an immunological response. Tuberculin, phytohemagglutinin, prodigiosine were used as inducers of the synthesis of cytokines. Heterodirection was found in the changes of elaboration of cytokines in similar immunological disorders in persons with different clinical forms of tuberculosis. Examination of patients with infiltrative tuberculosis indicated that the increased synthesis of TNF-alpha and IL-2 was to a greater extent associated with the activation of cell-mediated immunity and that of IL-1 beta with its inhibition. The relationships found between the production of cytokines and IgA and IgM levels are suggestive of their involvement in the regulation of immunoglobulin synthesis. Cytokine spectral alterations are associated with the changes in specific lymphocytic populations. In patients with infiltrative tuberculosis, the production of TNF-alpha and IL-1 beta was directly related to the proportion of CD4+ and CDS8+ and that of IL-2 is associated with the proportion of CD25+ and CD20+ and with the count of lymphocytes. At tuberculin stimulation of mononuclear cells, it is expedient to bear in mind the detection rate of cytokines and the level of their production. It was shown that the measurement of IL-1 beta, TNF-alpha, IL-2 may be used in the treatment of tuberculosis to assess the patients' immunological response and in the choice of immunomodulating therapy.

The authors investigated spontaneous and induced secretion of cytokins at different stages of generalized tuberculosis. In the development of infection there were inhibited IL-2 synthesis in response to ConA, emerging activity of PNO-alpha in response to the inductors in blood serum and culture of peritoneal macrophages, enhanced secretion of IL-6. Complete immunodeficiency was associated with cessation of IL-2 synthesis by splenocytes, elevated production of IL-6 by peritoneal macrophages, low concentrations of PNO-alpha in the serum and peritoneal macrophage cultures. In the treatment of M. bovis-infected mice with antibacterial drugs alone IL-6 secretion by peritoneal macrophages and PNO-alpha activity in the serum were increased. Immunocorrection resulted in marked activation of IL-2 production by splenocytes in response to ConA as well as enhanced synthesis of IL-6 in unstimulated cultures of peritoneal macrophages.

Human recombinant IL-1 beta injected intraperitoneally into CBA mice dose-dependently induced leukocytosis, stimulated phagocytosis and reduced tetrazolium nitroblue by peritoneal leukocytes, colony formation by bone marrow cells, enhanced Con A and IL-2-induced proliferation and IL-2 production in thymocytes and splenocytes. Recombinant IL-1 beta restored bone marrow cell proliferation reduced after 5-fluorouracil treatment and significantly increased the survival rates of lethally irradiated mice.

IL-1 and hydrocortisone have an opposite and competitive effect on the lymphocyte proliferation in cell culture. In mice recombinant human IL-1 beta dose-dependently induces high level serum corticosterone. Injection of IL-1 beta or hydrocortisone led to a similar alterations in the thymus: reduction of cellularity and decrease in spontaneous thymocyte proliferation. On the other hand in the same doses IL-1 beta stimulates spleen cell proliferation. IL-2 production and enhances serum antibody titres and the number of antibody producing cells in spleen of mice immunized with T-dependent antigen.

The spontaneous and induced production of monokin-interleukin-1 (IL-1) by the peripheral blood monocytes under the influence of autotransfusions of hemosorbent-treated blood (AHTB) was studied in 22 patients with an unfavorable course of ulcer disease. The spontaneous production of IL-1 was found to grow successively after a course of AHTB in patients with ulcer disease with terms of cicatrization more than 2 weeks. In patients with slow cicatrization of ulcers the IL-1 production did not change.

The spontaneous and induced production of monokine++-interleukin-1 (IL-1) by the peripheral blood monocytes under the influence of autotransfusions of hemosorbent-treated blood (AHTB) was studied in 22 patients with an unfavorable course of ulcer disease. The spontaneous production of IL-1 was found to grow successively after a course of AHTB in patients with ulcer disease with terms of cicatrization more than 2 weeks. In patients with slow cicatrization of ulcers the IL-1 production did not change.