[A comparative analysis of two methods for assessing the proinflammatory activity of monocytes in patients with juvenile depression]. / Sravnitel'nyi analiz dvukh sposobov otsenki provospalitel'noi aktivnosti monotsitov pri depressii u bol'nykh yunosheskogo vozrasta.

OBJECTIVE: To show that the results of evaluation of monocyte pro-inflammatory activity (PA) in patients with juvenile depression and healthy donors, obtained using a new method developed by us for counting the relative number of large monocytes on a multifunctional counter and cell analyzer, are similar to the results obtained using a standard assessment of the level of proinflammatory CD14+/CD16+ - monocytes on a flow cytofluorimeter. MATERIAL AND METHODS: The PA of monocytes, isolated from the peripheral venous blood of 18 patients with juvenile depression and 12 mentally and somatically healthy age and gender-matched persons was evaluated in two ways: using the generally accepted method of determining the relative number of monocytes with the proinflammatory phenotype CD14+/CD16+ on a flow cytofluorometer FC-500 and by counting the relative number of large monocytes on a multifunctional counter and cell analyzer Multisizer MS-4. PA of monocytes in patients was studied by using both methods in different variants: in the general group and in the subgroups of patients with low and high levels of active monocytes. RESULTS: The levels of monocyte PA determined in patients using the two methods did not statistically differ from each other in all variants of the analysis (p=0.6). The equivalence of the obtained results was confirmed by the Chi-square test (r=0.77, p=0.05), as well as by the detection of a statistically significant positive correlation between the number of monocytes with the pro-inflammatory CD14+/CD16+ phenotype, on the one hand, and the relative number of large monocytes, on the other hand (Spearman r=0.75; p<0.05). At the same time, a comparative analysis of the level of monocyte PA in the general groups of patients and healthy controls revealed significantly higher values of this indicator in patients compared with healthy persons when evaluated by both methods (p<0.05). Definition of monocytes PA using the new method developed by us for counting the relative number of large monocytes on the analyzer and cell counter is more economical and easier to perform, since it does not require the use of expensive devices and reagents, as well as complex device settings and a high level of operator qualification, as in the common method, and is carried out only by two parameters: by counting the number of large monocytes with a diameter of 12.5 to 15 microns and the total number of monocytes with a diameter of 9 to 15 microns. CONCLUSION: The proposed method for assessing monocyte PA by counting the relative number of large monocytes on the cell counter and analyzer can be used to analyze the activity of monocytes for research purposes.

[Features of the immune system and the risk of endogenous psychosis at juvenile age].

OBJECTIVE: To study an immunological profile at prodromal and manifesting stages of endogenous juvenile psychosis. METHODS: Authors studied 77 patients, aged from 16 to 25 years. Patients were stratified into 2 groups. The first group included 39 patients without psychotic symptoms (prodromal group) and the second one -- 38 patients with the first episode of psychosis (psychotic group). A complex of immunological parameters included phagocyte activity, cytotoxic activity, natural killer lymphocytes, production of interleukins (IL-1, IL-4, IL-10 and γ-interferon), content of circulating immune complexes. These parameters were measured at baseline and after treatment. RESULTS: The changes in the immune system emerged at the very early stages of the disease. There was the activation of proinflammatory and anti-inflammatory interleukins, decrease in the phagocyte index and cytotoxic activity of natural killer lymphocytes. The high activity of IL-10 production, decreased levels of the cytotoxic activity of natural killer lymphocytes and reduced phagocyte index as well as the accumulation of circulating immune complexes are maintained during psychosis. CONCLUSIONS: The authors recommend to use immunomodulating drugs, along with psychotropics, at the very early stages of the disease to prevent poor outcome.

[The use of canonical correlation analysis for the evaluation of correlation strength between clinical and biological parameters].

We studied correlations between factors of inherent immunity and the effectiveness of therapy in patients with endogenous psychosis using the method of canonical correlations. There were strong significant (canonical R>0,8; p=0,02) positive correlations between the therapeutic effectiveness of neuroleptics (haloperidol and clozapine) and values of factors of inherent immunity in the group of 34 men with schizophrenia, aged from 16 to 34 years, with the first episode of psychosis. The effectiveness of treatment was assessed by the percentage reduction of total scores on the PANSS scale or scores on PANSS subscales (positive, negative and general psychopathology) at the beginning and the end (after 60 days) of the treatment. Initial parameters of factors of inherent immunity (levels of gamma-interferon production by T-lymphocytes, proportion of phagocytosing neutrophils and monocytes, and cytotoxic activity of lymphocytes - natural killers) contributed to 67,3%, or more than two thirds, of the variance of treatment effects. The contribution of inherent immunity factors was determined mainly by their similar effects on the reduction of positive and general psychopathological symptoms, with the minimal effect on the reduction of negative symptoms. The maximum correlation was found for weighting coefficients for inherent immunity factors estimated as 0,567 for the proportion of phagocytosing neutrophils and monocytes; 0,518 - for the levels of gamma-interferon production by T-lymphocytes and 0,334 - for cytotoxic activity of lymphocytes - natural killers. The authors suggest that the reduction of activity of the cell branch of inherent immunity develops before the disease manifestation. It creates conditions for the activation of latently persistent infections (the cytomegalovirus infection, in our case) in a patient's organism, with the formation of therapeutic resistance. The method described may be widely used in clinical and biological psychiatry and neurology.

[The influence of atypical neuroleptics on the immune system of patients with schizophrenia].

Humoral and cellular immunological parameters were studied in 59 schizophrenic patients and 38 healthy subjects. It was demonstrated that high level of circulating immune complexes is characteristic of the acute state (a relapse) of schizophrenia. The level of this parameter was higher in patients before treatment vs. healthy controls; after therapy with olanzapine this level decreased and did not differ from that of controls. The functional activity of immunocompetent cells (the phagocyte activity of neutrophiles and monocytes, the cytotoxic activity of natural killer lymphocytes, interleukin-2, and interleukin-10 production) did not depend on the clinical condition of the patients and the therapy and was significantly lower than that of controls both before and during the treatment. Attention should be paid to the fact that the level of IL-1beta production in schizophrenia patients did not differ from that of controls. After eight weeks of therapy the level of IL-1beta production increased significantly in all groups of patients and was significantly higher than that of controls during the whole observation period irrespectively of sex and patients' response to the therapy.

[Immunological indices in schizoaffective and affective psychoses]. / Izuchenie immunologicheskikh pokazatelei pri shizoaffektivnykh i affektivnykh prikhozakh.

Proliferative activity of peripheral blood lymphocytes has been studied in patients with schizoaffective (18) and affective (24) psychoses in 4 experimental variants: cultivation of blood lymphocytes isolated by centrifuging in the density gradient with fetal (1st variant) or autologic serum (2nd variant); cultivation of lymphocyte obtained in plasma sedimentation with fetal (3rd variant) and autologic serum (4th variant). A level of functional lymphocyte activity was significantly decreased in patients. The data obtained suggest that different mechanisms underlie this decrease. In schizoaffective psychosis, a disturbance of cell cooperative interaction in immune response was observed. In affective psychosis, the determining factors were a decrease of the ability of lymphocytes to respond to mytogenic stimulation and a presence of the factor inhibiting a functional activity of lymphoid cells in patient's blood. Besides, it was shown that in patients with schizoaffective psychosis, lymphocyte proliferative activity inversely correlates with the disease duration and in affective patients the direct correlation between these indices was detected.

[A change of immune profile of patients with schizophrenia during treatment]. / Izmenenie immunnogo profilia bol'nykh shizofreniei v protsesse lecheniia.

Cellular and humoral immunological parameters have been studied in 59 schizophrenic patients and 38 healthy controls. Immunological indices (CIC, autoantibodies to cardiolipin) were found to be significantly elevated in patients in the acute disease stage before the treatment. After olanzapin therapy, a level of these parameters decreased and did not differ from that of controls. In patients, irrespective of clinical condition and treatment, functional activity of immunocompetent cells (phagocyte activity of neutrophils and monocytes, cytotoxic activity of lymphocytes natural killers, interleukin-2, interleukin-10 and gamma-interferon production), was significantly lower both before the treatment as after therapy, i.e. did not change during the whole study (28 weeks). In responders, a level of IL-1B production was higher than in controls before and during the treatment. In non-responders, it was similar to that in controls before the therapy, and increased during the treatment to a higher level.

[Interleukin system in schizophrenics]. / Sistema interleikinov u bol'nykh shizofreniei.

Interleukines (IL) levels, mononuclear phagocytes (MP) activity and proliferative T-lymphocytes activity were studied in 6 patients with paranoid (ICD-10 item F20.00) and 20 patients with shift-like (F20.01) types of schizophrenia. Significant (p < 0.05) decrease of MP activity, monocytes-stimulated IL-1 beta production (mostly pronounced in paranoid type) lymphocyte-stimulated IL-2 production (p < 0.05) and proliferate T-lymphocytes activity (p < 0.01) were characteristic of schizophrenia in use of low mitogen doses. A significant increase (p < 0.001) of IL-2 serum concentration was found only in shift-like type. The changes of IL-2 concentration are more frequent in younger patients, aged up to 30 years, with relatively long duration of illness and manifestation stage (over 5 years). An increase of serum IL-2 in the patients was not connected with the changes of soluble IL-2 receptors in the serum as it did not differ from the control values.

[The functional activity of the lymphocyte subpopulations in patients with schizophrenia and schizoaffective psychosis]. / Funktsional'naia aktivnost' subpopuliatsii limfotsitov u bol'nykh shizofreniei i shizoaffektivnym psikhozom.

The functional activity of natural killer (NK) and of T-helper (TH) lymphocytes was examined both in 19 patients with schizophrenia and in 6 patients with schizoaffective psychosis as well as in 93 control individuals. The patients were examined both before the treatment and two months after it. The cytotoxic level of NK lymphocytes was considerably decreased in all the patients before the treatment. The TH activity was decreased in 8 of 17 schizophrenic patients and in 1 of 4 schizoaffective patients observed during the acute period. The increase of cytotoxic NK activity was seen in patients with schizoaffective psychosis after the treatment while such alterations in schizophrenic patients were absent. The TH activity changed neither in schizophrenic nor in schizoaffective patients after the treatment.

[The immune system characteristics during normal aging and in Alzheimer's disease]. / Osobennosti immunnoi sistemy pri normal'nom starenii i pri bolezni Al'tsgeimera.

The paper presents a review of data available in the literature and the authors' own findings on age-related physiology and pathology of the immune system. Almost all parameters characterizing the functional activity of the immune system in Alzheimer's disease (AD) were demonstrated to significantly differ from those in the healthy elderly, The magnitude of immunological changes clearly correlated with the severity of dementia in AD patients. A hypothesis of the gradual development of immunological changes in an AD patient in relation to his dementia formation is given.

[The neuroimmune relationships during normal aging and in Alzheimer-type dementias]. / Neiroimmunnye otnosheniia pri normal'noi starenii i dementsiiakh Al'tsgeimerovskogo tipa.

Relationships between neurophysiological and immune parameters were studied in normal middle-aged and elderly subjects and in patients with dementia of Alzheimer's type (DAT). The rate of such interaction was minimal in normal aging, in DAT neuroimmune relations increased. The correlation between the immune parameters and the characteristics of components of visual evoked potentials and auditory brain-stem responses suggests that in the middle-aged healthy subjects, a primary role in neuroimmune relations belongs to limbicoreticular structures and to the mesencephalon. In normal aging, the influence of limbicoreticular structures on immune structures decreases. In DAT, the modulation of immune processes by limbicoreticular and thalamocortical structures, as well as the pontobulbar part of the brain stem increases. In middle age and in DAT, persons with different functional brain asymmetry (as estimated from electrophysiological criteria) have different lymphocytic functional activities and rates of neuroimmune interactions.

[Changes in the immunological parameters in Alzheimer's disease: their relation to disease severity]. / Izmenenie immunologicheskikh parametrov pri bolezni Al'tsgeimera: sviaz' s tiazhest'iu zabolevaniia.

The peculiarities of the immune system in patients with Alzheimer's dementia (AD) and their relations with some clinical parameters were investigated. 21 patients with AD aged 51-70 and 16 age-matched healthy subjects were included in this study. The following parameters were examined: 1) total lymphocyte numbers, 2) the functional activity of T- and B-lymphocytes under conditions of stimulation by nonspecific mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM) and 3) the production of interleukin-1 (IL-1) and interleukin-2 (IL-2). A statistically significant decrease (p < 0.01) in lymphocyte number and significant increase of proliferative activity of T-lymphocytes, stimulated by PHA (when the small mitogen doses in the range of 1.25-2.5 mg/ml were used) were found in patients with moderate and severe dementia (p < 0.05, p < 0.01). No significant changes of lymphocyte proliferative activity were detected in patients with mild dementia. Some tendency for higher IL-1 production was found in AD patients, but it was not statistically significant. No changes of functional activity of B-cells and of production of IL-2 in AD patients were found in comparison with the control group.

[Changes in the functional activity of T-lymphocytes after administration of stelazine]. / Izmenenie funktsional'noi aktivnosti T-limfotsitov pod vliianiem stelazina.

It has been established that stelazine administered in the dose corresponding to the therapeutic one is capable of inhibiting the proliferative activity of T lymphocytes and production of IL-2 in experiments in vitro. It is assumed that decrease of these characteristics in schizophrenic patients is related to the systematic intake of neuroleptics.

[Disorders of interleukin 2 biosynthesis by peripheral blood lymphocytes in patients with schizophrenia]. / Narushenie sinteza interleikina-2 limfotsitami perifericheskoi krovi bo'lnykh shizofreniei.

The aim of this study was to investigate the interleukin-2 (IL-2) production in schizophrenic patients with different forms of disease and controls. 70 schizophrenic patients and 20 healthy subjects were studied. Results obtained have shown that the IL-2 production depend on the forms of disease and different forms of progression. The results showed normal IL-2 production in patients with most forms of progression and decreased IL-2 level in the group with least forms of progression of disease.

[Use of levamisole in the combined therapy of patients with slowly progressing juvenile schizophrenia]. / Ispol'zovanie levamizola v kompleksnoi terapii bol'nykh iunosheskoi maloprogredientnoi shizofreniei.

Immunomodulating drug Levamisole was studied as a component in the combined treatment of juvenile slow progredient schizophrenia. Apart from normalizing the immune parameters, the drug improved the patients' clinical conditions. Most prominent was its clinical effect in patients with immune system sensitive to the drug. The patient's condition ameliorated in relation with the features of his initial state. Treating the patients with depressive-asthenic states has yielded the best results. Weaker was the effect on patients with obsessive-phobic disorders. The least curable were senesto-hypochondriac and dysmorphophobic disorders with sensitive delusions of relation.

[Use of the immunomodulator levamisole in the complex treatment of juvenile schizophrenics with an unfavorable course]. / Ispol'zovanie immunomoduliatora levamizola v kompleksnoi terapii bol'nykh iunosheskoi neblagopriiatno tekushchei shizofreniei.

The authors investigated the effect of the immunostimulant levamisole on the immunological reactivity of schizophrenics and the resultant decrease in the therapeutic resistance of these patients toward psychotropic therapy. Thirteen patients with juvenile malignant continuously progressive schizophrenia were studied, using a double blind design of examination. The number of suppressor T-cells in patients treated with levamisole increased from 16.6% to 22.8% (p less than 0.001) which was not observed in patients on placebo. It has been demonstrated that the immunological parameters in patients with juvenile malignant continually progressive schizophrenia can be fully recovered. Yet, the changes observed in the clinical picture were heterogeneous and unremarkable. The experimental findings suggest that the use of levamisole may be more effective in patients with less progressive forms of the disease.

[Features of the B-lymphocyte population of patients with malignant continuously progressive juvenile schizophrenia]. / Osobennosti B-limfotsitarnoi populiatsii u bol'nykh zlokachestvennoi iunosheskoi nepreryvnotekushchei shizofreniei.

Using immunofluorescence techniques, the authors measured the peripheral levels of B-lymphocytes and the number of immunoglobulin-synthetizing cells in 16 patients with malignant juvenile continuously progressive schizophrenia and in 19 healthy donors. The schizophrenic patients showed elevated amounts of circulating B-lymphocytes--24.4% versus 15.9% in the healthy donors. Moreover, this elevation came about at the expense of lymphocytes carrying immunoglobulins G and M on their surface. The study of the immunoglobulin-synthetizing property of B-lymphocytes showed that B-lymphocytes in schizophrenic patients were more active. The blood of schizophrenic patients contained two times as many cells with cytoplasmic immunoglobulins as in the control group. Differences in the number of cells with cytoplasmic immunoglobulins became even more significant following cultivation of lymphocytes with polyclonal B-cellular PWM activator.

[Effect of treatment with psychotropic preparations on suppressor T-lymphocytes in juvenile continuously-progressing schizophrenia]. / Vliianie lecheniia psikhotropnymi preparatami na supressornye T-limfotsity pri iunosheskoi nepreryvnotekushchei shizofrenii.

The paper deals with the effect of psychotropic drugs on blood levels of suppressive T-lymphocytes in patients with continuously progressive schizophrenia. The patients were examined three times: the first sample of blood was taken after a long psychotropic therapy, the second 3 weeks after the discontinuation of the therapy and the third one 3 weeks after the resumption of treatment. The lowest levels of suppressory T-lymphocytes (averaging 16.3%) were observed during the first examination. Following the discontinuation of therapy the content of T-suppresspors increased to 21.3% (P less than 0.001) failing, however, to reach the mean level characteristic of normal donors (25.7%). The amount of suppressory T-lymphocytes decreased again after treatment resumption. It is concluded that one of the factors contributing to changes in the immunological status in patients with juvenile continuously progressive schizophrenia may be a long-term use of psychotropic drugs.