Search

Serum concentrations of antiinflammatory cytokines and growth factors were measured in 30 patients with chronic viral hepatitis (HCV), mainly HCV RNA, and 10 patients with liver cirrhosis (LC), classes B and C according to Child-Pew. Serum concentrations of tumor necrosis factor-alpha (TNF alpha), granulocytic-macrophagal colony-stimulating factor (GM-CSF), and growth-transforming factor-1 beta (TGF1 beta) were increased in 63.86 and 80% patients with HCV and LC, respectively, and differed significantly (p < 0.05) from the control. The level of TNF alpha positively correlated with the concentration of alanine aminotransferase (r = 0.14). A positive correlation between TGF1 beta and histologic activity index was detected (r = 0.16). Increased levels (p < 0.05) of IL-5, TNF alpha, and TGF1 beta were detected in LC patients in comparison with the control. Patients with LC concomitant with anemia had higher (though not significantly) concentrations of TNF alpha in comparison with patients without anemia. Increased levels of proinflammatory cytokines and growth factors in the sera of patients with HCV and LC indicate activation of immunocompetent cells, including mononuclear phagocytes. These data are in line with experimental findings, indicating an important role of the studied cytokines in the development of hepatic inflammation, fibrosis, and cytopenic syndromes.

Serum content of proinflammatory cytokines (IL-1 beta, IL-6, TNF-alpha) and growth factors (GM-CSF, TGF-1 beta) and expression of CD14 and CD95 antigens on peripheral blood monocytes before and after 12-day therapy with alpha-interferon were studied in 25 patients with chronic viral hepatitis C (VHC). The concentrations of TNF alpha, GM-CSF, and TGF-1 beta were significantly increased (p < 0.05) and coexpression of CD14+ and CD95+ antigens on monocytes was increased by 61% in VHC patients in comparison with the control. After 3 months of therapy with alpha-interferon, the content of TNF alpha, GM-CSF, and TGF-1 beta essentially decreased and that of IL-6 increased; this was paralleled by improvement of clinical and laboratory parameters and decrease of coexpression of CD14+ and CD95+ antigens on blood monocytes. Modulation of the functions of immunocompetent cells and changed production of cytokines are apparently one of the mechanisms of inhibitory effect of alpha-interferon on HCV infection. Study of proinflammatory cytokines and growth factors in the serum and expression of CD14 and CD 95 antigens on monocytes can serve as additional tests for evaluating the efficiency of interferon therapy in patients with VHC.

Aim: To examine hemopoiesis and to estimate proinflammatory cytokines in blood serum from 42 patients with chronic viral hepatitis (CVH) associated with 1-3 lineage cytopenia in the blood., Material and Methods: 42 patients with diagnostically complicated hematological picture suggestive of hemoblastosis were examined using standard tests, bone marrow puncture and trepanobiopsy, laparoscopy with biopsy of the liver and spleen, transcutaneous puncture biopsy of the liver under ultrasonic control, explorative laparotomy with splenectomy and liver biopsy and, on demand, laboratory tests for hemolysis, presence of antithrombocytic and antileukocytic antibodies, iron metabolism, karyological analysis of bone marrow cells was also made., Results: The majority of the patients were diagnosed to have chronic hepatitis C with low activity of hepatic inflammation and frequent (55%) absence of the diagnostic antibodies to hepatitis C virus in the serum. In 86% of cases blood cytopenia reflected uneffective hemopoiesis and in 14% of cases hemopoiesis hypoplasia was found., Conclusion: Uneffective hemopoiesis, high content of immune response cells-effectors in the bone marrow and high concentration of TNF in the serum indirectly evidence for a pathogenetic relationship of chronic HCV infection with cytopenic hematological syndromes.

Hemopoiesis and functional activity of monocytes were assessed in 30 patients with chronic myelomonocytic leukemia (CMML). Changes in haemogram in CMML are characterized by anemia, thrombocytopenia, normal or increased count of leukocytes with absolute monocytosis and increased count of young granulocytes. Bone marrow hemopoiesis is characterized by enhanced proliferation of cellular elements of granulocytopoiesis and monocytes, suppressed erythropoiesis and megakaryocytopoiesis. Dysplastic changes are most expressed in the erythrocytic stem cells. Studies of lysosomal enzymes showed their increased activity in monocytes of CMML patients.

Fever is an important component of immune response of the organism to various stimulating effects (trauma, infection, inflammation). This complex process comprises activation of monocytes/ macrophages, their synthesis and secretion of proinflammatory cytokines and realization of multiple biological effects of cytokines including growth stimulation and differentiation of hemopoietic cells. Recently, there has appeared a trend to growing number of cases with uncommon hyperthermia and 2-3 germ cytopenia in the blood. Activation of the macrophage system and hyperproduction of proinflammatory cytokines can be viewed not only as an essential mechanism of hemopoiesis stimulation but also as a potential cause of hemodepression. The paper analyzes the relations between high functional activity of the macrophage system and development of cytopenia in patients with persistent fever. Functional activity of the macrophage system was studied on the model of patients with tumors or reactive proliferations of monocytes-macrophages as the latter are the main sources of IL-1-cytokine--a mediator of human fever. To prove the suggested correlation and its significance, a correlation analysis was made of 29 clinical and laboratory parameters in 184 patients and 100 controls.

Standard (hemogram, routine biochemical indices) and non-standard hematological parameters reflecting monocytic-macrophagal system (MMS) function and antioxidant defense were investigated in 140 subjects who had worked in radionuclide-contaminated zone after the Chernobyl accident. As shown by measurements of iron serum metabolism, lysozyme, total interferon, CIC, chemiluminescence of venous blood mononuclear leukocytes, MMS in 50% of them underwent negative changes in suppressed antioxidant defense. Standard hematological findings registered abnormalities only in 8-27% of the examinees.

Morphological and cytochemical examinations of mononuclear phagocytes (MP) from venous blood leukoconcentrate were carried out in 25 patients with chronic monocytic leukemia, 7 patients with malignant histiocytosis, 3 patients with Langerhans' cell histiocytosis and 26 patients with reactive proliferations of the cells belonging to MP system associated with autoaggressive, infectious diseases or tumors. Morphofunctional features of MP from the patients with tumor and reactive histiocytosis may serve additional criteria in differential diagnosis of the diseases in which pathological process runs with participation of MP system cells.

Iron metabolism parameters (increased level of serum ferritin, appearance of an iron pool specifically unrelated to transferrin, reduced ceruloplasmin level, etc.) were found changed in subjects who participated in liquidation of Chernobyl power plant accident aftereffects. These shifts in iron metabolism are explained by reduced antioxidant activity of plasma and indicative of mononuclear phagocyte dysfunction, thus necessitating a dynamic monitoring of this population.

Langerhans cell histiocytosis (LCH) and histiocytosis class II (without Langerhans cells) were treated in 10 and 2 patients, respectively, with alpha-interferon preparations: recombinant alpha 2-interferon and two combined preparations containing natural alpha-interferon and immune response phase 1 cytokines. The patients' age ranged from 18 to 61 years, all of them had multiple lesions. Six of them exhibited dysfunctions of the affected organs. As shown by the results of 16-52-month follow-up, LCH patients' disease persisted in chronic active stage without progression (8 cases) or reached a complete remission (1 case), one patient died. In histiocytosis class II alpha-interferon administration was uneffective.

Difficulties in the morphological diagnosis of the diseases due to proliferation of mononuclear phagocyte system (MPS) cells have stimulated the search for additional differential-diagnostic criteria. The investigations were conducted in 10 malignant histiocytosis, 16 histiocytosis-X, and 34 reactive histiocytosis patients. The assay of serum ferritin was shown to have high informative value for clinical practice. The presence of extremely high hyperferritinemia in patients with morphologically verified histiocytic proliferations has evidenced a malignant character of the process.

A review of literature has been presented including current data on bone marrow genesis functional role of mast cells in the human body, as well as characteristics of the main clinical variants of mastocyte tumor proliferations (solitary mastocytoma, urticaria pigmentosa, generalized mastocytosis). Clinicomorphological picture and positive results of the treatment with the Soviet cytostatic spirobromine of two patients suffering from generalized mastocytosis are described.

A review of literature has been presented involving clinicomorphological characteristics of certain variants of histiocytosis X (HX) and current conception considering this disease as an immunopathologic process that is underlain by reactive proliferation of a specific subtype of antigen-presenting macrophages--Langerhans' cells. Clinico-morphological picture has been described and the results of successful treatment with roferon (human gene-engineering alpha 2-interferon) in 3 adult patients with HX have been presented. It is stressed that the actual effectiveness of the treatment with roferon could not be critically evaluated due to a high frequency of spontaneous remissions of this disease.

Clinicomorphologic features of the hyaline-vascular and plasmacytic variants of lymph nodes angiofollicular hyperplasia are defined on the basis of literature data and the authors' own observations. Problems of morphologic diagnosis and nosology of this kind of the lymph node lesion are discussed.

The authors have summarized the research data on lymphoid cells of the lymph nodes and peripheral blood of normal donors, patients with hematological nonlymphoproliferative diseases, reactive lymphadenopathies and malignant lymphoproliferative diseases (Hodgkin's disease, chronic lympholeukemia and lymphosarcomas). The data indicate that the use of the panel of the simplest tests of immunological phenotyping provides in many cases sufficient information for differential diagnosis of reactive lymphadenopathies and malignant lymphoproliferative diseases as well as for diagnosing the early stage of lymphosarcoma leukemization.

The effect of 17-oxyprogesterone capronate on the proliferative activity and metabolic processes in the endometrium of patients with glandular hyperplasia of the endometrium was studied. It was shown that the proliferative activity was inhibited while the secretory processes in the glandular epithelium were activated. This effect was achieved only after a long-term (6-9 months) administration of the hormone.