[Characteristics of A-interferon-generated dendritic cells in patients with pulmonary tuberculosis].

The phenotype of the dendritic cells (DC) generated from the adhesion fraction of mononuclear cells in the presence of GM-CSF and alpha-interferon was studied in patients with pulmonary tuberculosis. Despite the absence of significant differences in the count of mature CD83+DCs in the groups of patients (n = 38) and healthy donors (n = 30), elevated CD14(+)-monocyte levels and few activated CD25(+)-DCs were indicative of the impaired process of DC maturation/generation in patients with pulmonary tuberculosis, particularly in a subgroup of patients with a low T-cell proliferative response against PPD (PPD-anergy, n = 10). The patients with tuberculosis showed the lower relative levels of CD11c(-)-CD123(+)-DC and the normal levels of myeloid CD11c(+)D123(-)DCs. However, in patients with PPD-anergy, the content of myeloid CD11c(+)CD123(-)-DCs was significantly higher than that in PPD-reactive patients. Moreover, the patients with PPD-anergy were characterized by the elevated peripheral blood levels of CD14+CD16(+)-monocytes, which was associated with the high suppressive activity of monocytes (r(s) = 0.53; p < 0.05). The impaired process of DC generation/maturation in patients with pulmonary tuberculosis is believed to be associated with the changes in the phenotypic and functional properties of monocytes and to be a cause of an inadequate antigen-specific response in tuberculous infection.

[Immunological indices in gastric cancer].

Immunological indices were assayed in 167 patients with gastric cancer. Tumor growth involved reduction in levels of neutrophil peroxide (p<0.05), CD3+ and CD19+-cells (p<0.05) as well as intensification of apoptosis of lymphocytes (p<0.05). As monocytic and granulocytic phagocytosis (p<0.001) and HLA-DR-expression in monocytes (p<0.001) diminished, and mitogen-induced proliferative activity of mononuclear cells suppressed (p<0.05), total and relative levels of CD8+-cells (p<0.05) and spontaneous proliferative activity of mononuclear cells (p<0.05) in peripheral blood increased. Such changes should not be reganded as expression of immunosuppression alone. Mechanisms of immunological failure inherent in tumor growth need to be investigated further.

[Antigen-specific immunotherapy as a component of combined therapy for malignant brain tumors]. / Antigenspetsificheskaia immunoterapiia v kompleksnom lechenii bol'nykh zlokachestvennymi opukholiami golovnogo mozga.

The purpose of the present research was to study immunity in the course of complex treatment for malignant gliomas of the brain and to evaluate extracorporeal antigen-specific immunotherapy (EASIT), a pilot procedure which was carried out according to an approved protocol. Initially, lowered HLA-DR+ monocyte count and in vitro inhibition of proliferative activity were reported in all patients. Inductive EASIT started in early postoperative period aborted immune disturbances caused by surgery. In 1998-2000, the procedure was performed in 33 patients with anaplastic astrocytoma (AA) (20) and glioblastoma (GB) (13). Mean dose of cell infusion was 2.43(0.18 x 109/patient and was well tolerated. There are 22 survivors and 9 patients died (GB--4 and AA--5; overall mortality--29%). Mean relapse-free survival was 14.2 mo (22); stable remission during 12-18 mo--37.5% (3/8)(GB) and 64% (9/14) (AA) Complete rehabilitation of immunity was generally reported 12 mo after the course of EASIT. Hence, complex treatment (surgery + EASIT) enhanced its efficacy in the management of brain tumors.

[Characteristics and immunologic changes in patients with malignant brain tumors]. / Kharakteristika i mekhanizmy immunnykh narushenii u bol'nykh so zlokachestvennymi opukholiami golovnogo mozga.

The investigation was concerned with assaying immunity and evaluating the role played by monocytes and tumor cells in the formation of T-cell dysfunction in malignant glioma (MG). The study group included 28 patients with anaplastic astrocytomas (n = 18) and glioblastomas (n = 10). MG patients showed significant changes in the numbers of CD16+ NK-cells and HLA-DR monocytes as well as lowered levels of HLA-DR expression on monocytes and proliferative response of T-lymphocytes as compared with both standard and alternative pathways of activation. Monocytes and macrophages suppressed T-cell activity due to production of prostaglandins E2 in such patients. Enhanced immunosuppression was also reported in 24-hour supernatants of tumor cells. Immune disorders were shown to involve apoptosis-independent mechanisms. Hence, despite the immune privilege of the brain, immunocompetent cells crossed blood-brain barrier and counteracted with tumor cells. As a consequence, monocyte function and cellular cooperation dropped while production of immunosuppressive factors rose, and T-cell dysfunction was brought about through apoptosis-independent mechanisms.

[Surgical sepsis. II. Effectiveness of immune therapy with recombinant interleukin-2]. / Khirurgicheskii sepsis. Soobshchenie 2. Effektivnost' immunoterapii rekombinantnym interleikinom-2.

Two methods of administration of Roncoleukin were used as two subcutaneous injections in dose of 500,000 units with a 3 day interval and in the regimen of extracorporeal immunotherapy. The use of Roncoleukin resulted in the clinical improvement in 83% of patients and in the detoxicating and immunocorrecting effects in 77.3 and 60% respectively which was reliably different from analogous indices (33.4%, 45% and 7.5%) in the placebo group. Other values of the prognosed lethality being equal, the real 28-day lethality in the placebo group was 21.5%, while the using of Roncoleukin allowed the level of lethality of patients with surgical sepsis to become 3.8 times lower, including the subgroup of patients with severe sepsis from 50 to 13.6%. The trials performed showed the drug Roncoleukin to be endurable and not toxic and allowed to determine the indications and contraindications to using cytokin therapy in the complex treatment of pyo-septic diseases.

[Surgical sepsis. Part I. Immunologic markers of systemic inflammatory reaction]. / Khirurgicheskii sepsis. Chast' I. Immunologicheskie markery sistemnoi vospalitel'noi reaktsii.

The aim of the work was to develop accessible methods of laboratory diagnosis of the systemic inflammatory reaction, based on an assessment of biological (inflammatory and immunosuppressive) activity of serum of surgical sepsis patients (n = 104). The investigation has shown that surgical sepsis patients are characterized by marked immune dysfunctions, immunosuppressive bioactivity of blood serum being detected in most patients (in 65.6%) beginning from the earliest stages of the development of the sepsis process. It was found that in patients with dominating suppressive activity of serum the immune disturbances were more pronounced and in every second case they were of combined type. The authors propose to use the degree of the immunosuppressive potential of serum factors as the key classification sign determining the presence of CARS-positive or CARS-negative phenotype in such patients. The results obtained suggest that it is expedient for complex therapy of surgical sepsis to include immunocorrection aimed at the weakening of immunosuppresive action of antiinflammatory mediators and shift of the balance towards the reinforcement of activity of proinflammatory ones (IL-12, IL-1) and Th-1 cytokines (IL-2, IFN-g).

[Immunomodulating effect of locoregional cytokine therapy in patients with pulmonary tuberculosis]. / Immunokorrigiruiushchii éffekt lokoregional'noi tsitokinoterapii u bol'nykh tuberkulezom legkikh.

The immunomodulating effect of local and regional cytokine therapy was studied in patients with different forms of pulmonary tuberculosis. The signs of immunosuppression either preserve or progress with tuberculostatic chemotherapy (a control group). The inclusion of cytokine therapy into a treatment regimen for patients with pulmonary tuberculosis (an experimental group) assures complete correction of immune disorders in 30% of patients, as manifested by a significant increase in the absolute count of T lymphocytes, in the relative content of CD8 cells and monocytes with HLA-DR antigen expression. The most pronounced effect was achieved in patients with a fibrocavernous form of pulmonary tuberculosis. Immunological correction was accompanied by positive clinical and laboratory changes. Arrested intoxication, improved X-ray pattern of the lung, and ceased bacterial isolation were recorded in the patients. Positive clinical and immunological changes suggest that it is expedient to include local and regional cytokine therapy as part of treatment in patients with pulmonary tuberculosis.

[Cytokines in the treatment of a generalized surgical infection]. / Tsitokiny v lechenii generalizovannoi khirurgicheskoi infektsii.

A novel approach to the treatment of surgical sepsis has been tried: cytokine-based immunotherapy. Human recombinant interleukin-2 (IL-2) and a mixture of native cytokines obtained by arteriovenous perfusion of xenospleen were used as a source of proinflammatory cytokines. Extracorporeal immunotherapy of 62 patients with surgical sepsis with mononuclear cells treated by autologous IL-2 resulted in a significant decrease of endotoxicosis and effective immunocorrection. Cytokine-based immunotherapy notably decreased the mortality of patients with generalized surgical infection--to 14.6%, which was lower than the expected mortality (35%) and the mortality in the control group (34.5%).

[Specific features of immunity in patients with different forms of pulmonary tuberculosis]. / Osobennosti immuniteta u bol'nykh s razlichnymi formami tuberkuleza legkikh.

The cellular immunity was studied in 59 patients with pulmonary tuberculosis. The development of tuberculous infection was ascertained to be accompanied by decreases in the relative counts of CD9, CD8, and CD72 lymphocytes, as well as monocytes, expressing class II histocompatibility antigens (DR). The patients with tuberculosis were found to have suppressed proliferative T-cell activity and IL-2 production, moderately decreased IL-1 production and increased TNF alpha secretion.

[Cytokines in the treatment and prevention of postoperative infectious complications in patients with colorectal cancer]. / Tsitokiny v lechenii i profilaktike infektsionnykh posleoperatsionnykh oslozhnenii u bol'nykh kolorektal'nym rakom.

Surgery for colorectal carcinoma has supplemented the following cytokine-based procedures: (1) extracorporeal immunotherapy (EIT) with autologous rIL2-activated mononuclear cells for treatment of patients with infectious complications, and (2) extracorporeal infusion immunotherapy with native cytokines (perfusate of xenospleen) to prevent postoperative infectious complications. EIT was followed by an effective correction of T-cell immunodeficiency and rehabilitation of monocytic function; rapid decrease in symptoms of endotoxicity; improved response to conventional therapy, and, as a result, a fall in mortality rates (from 38.9 to 11.7%). Immunotherapy with native cytokines brought about a significant decrease in postoperative complication incidence (36.4-15.8%), the average length of stay in hospital falling by 6.8 days. Immunological correction with cytokines was instrumental in raising the efficacy of surgical treatment of colorectal tumors.

[Preparation of hybrid proteins consisting of human interleukin-2 and the cytotoxic A-subunit of Shigella toxin]. / Poluchenie gibridnykh belkov, sostoiashchikh iz interleuikina-2 cheloveka i tsitotoksicheskoi A-sub''edinitsy toksina shigelly.

Recombinant plasmids providing the synthesis of chimeric proteins consisting of amino acid sequences of human interleukin-2 (IL-2) and Shiga toxin cytotoxic A-subunit (ILA and AIL chimeric toxins) were constructed. The ILA and AIL chimeric toxins were shown to inhibit protein synthesis in the rabbit reticulocytes cell-free system. These chimeric toxins displayed two opposite activities of the constituent parts of their molecules on T-lymphocytes from the peripheral blood of healthy volunteers. Hybrid protein AIL (approximately 10(-6) g/ml) has caused the most significant depression of T-lymphoblast proliferation.