Цель. Изучить закономерности изменения экспрессии интерлейкина-10 и интерлейкина-24, обладающих иммуномодулирующим эффектом, при развитии B-клеточного хронического лимфолейкоза. С учетом этого выявить информативные прогностические критерии развития гемобластоза и/или нового подхода к терапии заболевания. Методы. У 120 больных с разными стадиями В-клеточного хронического лимфолейкоза методом твердофазного иммуноферментного анализа исследована динамика уровней интерлейкина-10 и интерлейкина-24 в сыворотке крови. Результаты. Обнаружено закономерное повышение содержания интерлейкина-10 и интерлейкина-24 в сыворотке крови пациентов уже на начальной стадии B-клеточного хронического лимфолейкоза и сохранение их достоверно высоких уровней на последующих стадиях заболевания. Заключение. Обнаруженный нами факт повышения содержания интерлейкина-10 в сыворотке крови пациентов с В-клеточным хроническим лимфолейкозом является фактором риска снижения противоопухолевой защиты организма вследствие подавления им механизмов клеточного иммунитета и способности ингибировать апоптоз малигнизированных клеток. Напротив, повышение экспрессии интерлейкина-24, обладающего проапоптотической активностью и стимулирующего дифференцировку клеток, может способствовать повышению эффективности механизмов противоопухолевой резистентности организма. Устранение дисбаланса продукции и/или содержания указанных цитокинов в сыворотке крови может создать условия повышения эффективности терапии пациентов с В-клеточным хроническим лимфолейкозом. Aim. To study serum levels of immunosuppressive cytokines (interleukin (IL)-10 and IL-24) in patients with B-cell chronic lymphocytic leukemia for assessment of the disease progression and elaboration of a new treatment strategy. Methods. 120 patients with B-cell chronic lymphocytic leukemia were enrolled in the study and divided into four groups according to the disease stage (Rai stage I-IV). Control group included 30 healthy volunteers. Concentrations of IL-10 and IL-24 were measured in serum using the enzyme-linked immunosorbent assay (ELISA). Results. Serum levels of IL-10 and IL-24 levels were significantly increased in all patient groups compared to the control. No difference in the cytokines levels between the patient groups was observed. Conclusion. In patients with B-cell chronic lymphocytic leukemia, the increased serum level of IL-10 might impair the antitumor defence by inhibiting the cell immune response and preventing apoptosis of malignant lymphocytes. On the other hand, the increased serum level of IL-24 might oppose these effects by promoting cellular differentiation and inducing apoptosis in malignant cells. Therefore, correction of IL-10/IL-24 imbalance may be a beneficial therapeutic strategy for patients with B-cell chronic lymphocytic leukemia.
The article evaluates balance of growth-stimulating and growth-inhibiting factors in blood serum of patients with different stages of B-cell chronic lymphatic leukemia residing on examination and hospital treatment in Saratov clinic of occupational pathology and hematology in 2007-2016. The indices of content of VEGF165, PDGF-AB, pRb, p53 and p73 in blood serum was detected using solid-phase enzyme-linked immunosorbent assay. The specific characteristic of B-cell chronic lymphatic leukemia became stably higher content of growth-stimulating cytokines of development of disease that permitted to conclude about (VEGF165, PDGF-AB) in dynamics of development of disease that permitted to conclude about their important role in mechanisms of oncogene transformation and stimulation of proliferation activity of neoplastic cells at various stages of pathology. At the same time, disturbance of anti-proliferation signals under B-cell chronic lymphatic leukemia was characterized by singleat-once decreasing of controlling cell cycle of several mechanisms of regulation of changing G1-phase to S-phase conditioned by low level of inhibitors of cyclin-dependent kinases (p53 and p73) and inadequate expression of regulator of cellular cycle of protein pRb.
The research work presents results of clinical laboratory investigations of dynamic changes of immune phenotype of B-lymphocytes in different stages of B-cell mode of chronic lymphocytic leukemia. The detection of the content of CD-marker molecules in 60 patients with different stages of B-cell mode of chronic lymphocytic leukemia (0-I, II, III, IV according K.R. Rai et al. classification, 1975) was conducted. Investigation of the character of expression of marker molecules (CD19, CD5, CD20, CD23, CD38) on B-lymphocytes of peripheral blood with using of standard panel of monoclonal antibodies for flow cytometry «Facs-Calibur» (BD, USA, 2006) was carried out. The examination of patients with this pathology reveals some regularities of changes of immune phenotype of B-lymphocytes which were parallel with stages of the disease. The appearance of atypia of B-lymphocytes characterized by co-expression of CD19 and CD5 as well as significant activation of B-cells characterized by expression of CD23 and CD38 were observed.
В работе проведена оценка функциональной активности эндотелия у больных с различными стадиями В-клеточного варианта хронического лимфолейкоза, находящихся на обследовании и стационарном лечении в клинике профпатологии и гематологии г. Саратова в период с 2007 по 2013 гг. Критериями функциональной активности эндотелия явились показатели содержания в крови эндотелина-1 и ангиотензина-II, определяемых с использованием твердофазного иммуноферментного анализа. Как оказалось, характерной особенностью хронического лимфолейкоза явилось прогрессирующее повышение содержания в сыворотке крови эндотелина-1 и ангиотензина-II, обнаруживающее параллелизм со стадиями развития заболевания. Выявленные нами признаки эндотелиальной дисфункции могут быть использованы в качестве дополнительных диагностических и прогностических критериев прогрессирующего течения В-ХЛЛ.
ГБОУ ВПО «Саратовский Государственный медицинский университет им. В.И. Разумовского Минздрава России», Саратов, e-mail: zhevakt@rambler.ru В работе проведена оценка функциональной активности эндотелия у больных с IV стадией В-клеточного варианта хронического лимфолейкоза, находящихся на обследовании и стационарном лечении в клинике профпатологии и гематологии г. Саратова в период с 2007 по 2013 гг. Критериями функциональной активности эндотелия явились содержание в крови растворимых адгезивных молекул (Е-селектина, ICAM1), метаболита оксида азота – нитрита азота, гомоцистеина и протеина С, определяемых с использованием твердофазного иммуноферментного анализа. Как оказалось, характерной особенностью терминальной стадии хронического лимфолейкоза явилось повышение уровней в сыворотке крови растворимых адгезивных молекул (Е-селектина, ICAM-1), гомоцистеина, увеличение активности NO-синтазной системы при одновременном снижении содержания протеина С. Усиление экспрессии эндотелиально-лейкоцитарных адгезивных молекул является одним из молекулярно-клеточных механизмов развития инфильтративных изменений в различных органах и тканях. Одним из патогенетических факторов нарушения функциональной активности эндотелия можно считать возрастание содержания гомоцистеина, обладающего способностью вызывать дезорганизацию структуры сосудистой стенки. Выявленные нами признаки эндотелиальной дисфункции могут быть использованы в качестве дополнительных диагностических критериев развития терминальной стадии хронического лимфолейкоза. Ключевые слова: В-клеточный вариант хронического лимфолейкоза, Е-селектин, ICAM-1, оксид азота, гомоцистеин.
We have done the analysis of endothelial functional activity in patients with stage IV of B-cellular variant of chronic lymphocytic leukemia. Criteria of endothelial functional activity were the levels of adhesive molecules (Е-selectin, ICAM-1), nitric oxide metabolites, homocysteine, and protein C which were detected by enzyme multiplied immunoassay method. It has been revealed that characteristic peculiarity of terminal stage of B-cellular variant of chronic lymphocytic leukemia is increased levels of soluble adhesive molecules (Е-selectin, ICAM-1), homocysteine in blood serum, elevated activity of NO-synthase system, and decreased level of protein C. Intensified expression of endothelial-leucocytic adhesive molecules is one of the molecular-cellular mechanisms of the lymphocytic infiltration of different organs and tissues. Elevation of homocysteine levelis one of the pathogenic factor of endothelial functional abnormality. The features of endothelial dysfunction revealed by us may be used as additional diagnostic criteria of the development of terminal stage.
The article presents the results of study of cytokine profile of blood of patients with B-cell lymphatic leukemia. It is established that at diferent stages of disease the regular characteristic of changes in cytokine status is the increase of concentration of interleukin 4 (IL=4) and tumor necrosis factor This fact can be considered as one of leading pathogenic factors leading to disturbances of intercellular interaction in lymphoid tissue and to development of systemic metabolic and functional disorders. The parallelism between progressing increase of concentration of interleukin 4 and a-tumor necrosis factor character of qualitative and quantitative alterations of cell structure of peripheral blood, severity of clinical manifestations of disease are established. The indicators of concentration of interleukin 4 and a-tumor necrosis factor in blood are the objective diagnostic and prognostic criteria ofpathology development. They can complement the classification attributes of staging of the course of chronic lymphatic leukemia.
The article presents the results of study of cytokine profile of blood of patients with B-cell lymphatic leukemia. It is established that at different stages of disease the regular characteristic of changes in cytokine status is the increase of concentration of interleukin 4 (IL=4) and tumor necrosis factor. This fact can be considered as one of leading pathogenic factors leading to disturbances of intercellular interaction in lymphoid tissue and to development of systemic metabolic and functional disorders. The parallelism between progressing increase of concentration of interleukin 4 and a-tumor necrosis factor, character of qualitative and quantitative alterations of cell structure of peripheral blood, severity of clinical manifestations of disease are established. The indicators of concentration of interleukin 4 and a-tumor necrosis factor in blood are the objective diagnostic and prognostic criteria of pathology development. They can complement the classification attributes of staging of the course of chronic lymphatic leukemia.
The research work presents an analysis of results of investigations of cytokine blood profile in the patients with B-cellular chronic lymphoid leukemia. Regular peculiarity of cytokine status change at different stages of chronic lymphoid leukemia is increased IL-10 and TNF-α levels in serum what may be the most important pathogenetic factor of intercellular interaction abnormality in lymphoid tissue in the chronic lymphoid leukemia development. Parallelism between progressive TNF-α increase and severity aggravation of pathology has been determined. IL-10 and TNF-α blood content indications may be used as objective diagnostic and prognostic criteria of pathology, and in the evaluation of effectiveness of complex therapy of this disease, as well as may add existing classification signs of chronic lymphoid leukemia severity.
The aim of the research is to study and to analyze results of investigations of cytokine blood profile in patients with B-cellular chronic lymphocytic leukaemia. Materials and methods: Complex investigation of 60 patients with B-cellular chronic lymphocytic leukaemia has been carried out. Patients have been randomized into 4 groups of observation according to the severety of disease (classification of Rai K. R., 1975). Accepted methods of somatic status and he-matologic indices as well as method of flow cytometry for establishment of B-lymphocytes immune phenotype have been used. Cytokine levels were detected by enzyme immunodetection. Results: Regular peculiarity of cytokine status change in different forms of chronic lymphocytic leukaemia development has been an increase of interleukine-4, interleukine-6, interleukine-7, interleukine-10 and tumor necrosis factor-alpha levels in serum that is one of the main pathogenetic factor of intercellular interaction abnormality in lymphoid tissue in the chronic lymphocytic leukaemia development. Conclusion: Increased indications of cytokines content in blood may be used as diagnostic criteria of pathology severity and in evaluation of effectiveness of complex therapy of the disease, as well as a classification sign of severity of chronic lymphocytic leukaemia
The aim of the research is to study and to analyze results of investigations of cytokine blood profile in patients with B-cellular chronic lymphocytic leukaemia. Materials and methods: Complex investigation of 60 patients with B-cellular chronic lymphocytic leukaemia has been carried out. Patients have been randomized into 4 groups of observation according to the severety of disease (classification of Rai K. R., 1975). Accepted methods of somatic status and he-matologic indices as well as method of flow cytometry for establishment of B-lymphocytes immune phenotype have been used. Cytokine levels were detected by enzyme immunodetection. Results: Regular peculiarity of cytokine status change in different forms of chronic lymphocytic leukaemia development has been an increase of interleukine-4, interleukine-6, interleukine-7, interleukine-10 and tumor necrosis factor-alpha levels in serum that is one of the main pathogenetic factor of intercellular interaction abnormality in lymphoid tissue in the chronic lymphocytic leukaemia development. Conclusion: Increased indications of cytokines content in blood may be used as diagnostic criteria of pathology severity and in evaluation of effectiveness of complex therapy of the disease, as well as a classification sign of severity of chronic lymphocytic leukaemia
