[The use of statins, a new approach to the treatment of autoimmune diseases].

HMG-CoA inhibitors (statins) are widely used for the prevention of cardiovascular events and the management of hypercholesterolemia. Recently, multiple cholesterol-independent properties of statins have been discovered. The present review focuses on immunomodulatory and anti-inflammatory effects of statins and their implications for the treatment of autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, and psoriasis.

[Simvastatin effects on the disease activity and cholesterol content in blood serum lipoprotein subfractions in patients with rheumatoid arthritis].

AIM: To study activity of rheumatoid arthritis (RA) and cholesterol content in subfractions of blood serum lipoproteins in the course of simvastatin treatment. MATERIAL AND METHODS: The pilot study enrolled 16 patients with active rheumatoid arthritis (RA) meeting ACR criteria. Any standard anti-RA medication in stable doses was supplemented with simvastatin in a dose 40 mg/day for 12 weeks. The response was assessed by contents of cholesterol in serum lipoprotein subfractions and DAS28 index. RESULTS: At the end of the treatment course there was a significant elevation of HDLP2 and HDLP3 cholesterol and reduction in the levels of LDLP1-3 and LDLP cholesterol. DAS28 decreased by 0.89 points to the end of the treatment. CONCLUSION: Administration of simvastatin in patients with active RA on standard disease-modulating drugs has an antiatherogenic action and attenuates the disease activity. These pilot data should be confirmed by further large-scale controlled trials.

[Relationship between blood lipid spectrum and activity of the disease in patients with rheumatoid arthritis].

Patients with rheumatoid arthritis (RA) are at risk of cardiovascular disorders. Pathogenesis of rapidly developing atherosclerosis in RA remains to be elucidated. The aim of this study was to compare cholesterol content in serum lipoprotein subfractions in patients with RA and healthy subjects and to establish relationship between lipid profile variations, severity of the disease, and plasma levels of anti-inflammatory cytokines. The study included 15 patients with active RA and 120 healthy subjects of comparable sex and age. RA was found to be associated with a significant decrease of cholesterol of high density (HDL2) and intermediate density (IDL) lipoproteins and its elevation in low density lipoproteins (LDL1-3). There was negative correlation between the latter parameter and disease activity index. No relationship between lipoprotein cholesterol and serum interleukins (IL-6, IL-8) TNF-alpha, and IFN-gamma) was documented. It is concluded that patients with RA exhibit proatherogenic changes of cholesterol content in different lipoprotein subfractions related to the severity of the disease. Further studies are needed to elucidate molecular mechanisms of dyslipidemia in RA and to ensure the choice of optimal targets for therapeutic modalities reducing the risk of cardiovascular disorders.

[Results of Befnorin clinical trails in healthy volunteers]. / Rezul'taty klinicheskogo ispytaniia preparata benforina na zdorovykh dobrovol'tsakh.

Clinical trails of Befnorin based on the human recombinant TNF-beta elaborated at the Research Design and Technology Institute of Biologically Active Substances, "Vector" State Research Center of Virology and Biotechnology, were carried out on healthy volunteers in compliance with a decision passed by the Committee of Medical and Immunobiological Preparations, Russia's Health Ministry. Single Befnorin doses of 5-10(4) U, 10(5) U, 5-10(5) U, and 10(6) U were administered as intramuscular injections. Clinical, biochemical and immunological parameters were registered for 7 days after a single dose. The drug had an impact on the below immunity indices: Fc-phagocytosis of monocytes, migration index and migration inhibition index. The dose of 10(5) U was proven to be most effective and safe. Supposedly, the drug can be effective in the treatment of herpetic diseases.

[The effect of new biologically active substances on effector T-lymphocytes in vitro]. / Vliianie novykh biologicheski aktivnykh veshchestv na éffektornye T-limfotsity in vitro.

Levamisole has been demonstrated to stimulate the activity of T effectors in patients with rheumatic arthritis directly and indirectly via production of the factors influencing effector functions. The organosilicon compound minval was beneficial both in patients and donors. Its activity was mediated by the production of factors in donors, whereas in patients it showed direct and indirect actions, being higher than that of levamisole. The bioflavonoid derived from the Rosa L. root was shown to exert no action on T-effector function.

[The immunopharmacodynamics of mival]. / Izuchenie immunofarmakodinamiki mivala.

The authors studied in vitro the immunopharmacodynamics of the new silantrane mival. It was shown that mival possessed mitogenic effects on mononuclear cell proliferation in donors and patients with rheumatoid arthritis. The drug stimulated mononuclear cell proliferation, by acting selectively on T lymphocytes, enhancing T-cell growth lymphokine production, T-suppressor cell activity, and inhibiting prostaglandin E2 production.

[The effect of kobazol and atsizol on the proliferation of mononuclear cells]. / Vliianie kobazola i atsizola na proliferatsiiu mononuklearnykh kletok.

The authors studied the new imidazole-containing drugs cobazole and acizole for their effects on the proliferation of mononuclear cells from donors and patients with rheumatic arthritis. Acizole was found to produce no effects on mononuclear cell proliferation, whereas cobazole inhibited only the increased spontaneous proliferation of mononuclear cells in patients with rheumatic arthritis, which was due to a higher activity of nonspecific T-suppressor lymphocytes.

[The immunoactive properties of trekrezan]. / Immunoaktivnye svoistva trekrezana.

It was shown that in vivo trecrezan possessed strong immunoactive properties: it decreased the spot-forming activity of polypotent stem blood cells, stimulated lympho- and hemopoesis, antibody formation, possessed steady antiinflammatory activity. It stimulated in vitro mononuclear cell proliferation in man due to its direct action on B lymphocytes and increase in lymphokine and monokine production.

[The problem of secondary immunodeficiencies in patients with chronic bronchitis]. / Problema vtorichnykh immunodefitsitov u bol'nykh khronicheskim bronkhitom.

The paper concerns the problem of secondary immunodeficiency (SID) in chronic bronchitis (CB) patients. Clinical and laboratory criteria of SID are suggested with clinical illustrations covering 57 cases. SID was diagnosed in 80.7% of the examinees and was associated with reduced quantitative and functional parameters of T-lymphocytes, imbalance in subpopulations of regulatory T-lymphocytes. Observations of the patients during their treatment with immunostimulants showed the changes to be reversible, accompanied frequently with parallel rise in serum immunoglobulins, circulating immune complexes.

[Immunological disorders in different clinical variants of rheumatoid arthritis]. / Immunologicheskie narusheniia pri razlichnykh klinicheskikh variantakh revmatoidnogo artrita.

The authors present the current data on the disorders of immune functions in patients suffering from rheumatoid arthritis (RA). Provide evidence for the pathogenetic heterogeneity of the known clinical patterns of RA, mainly seronegative and seropositive varieties, with special reference to the differences in the lowering of the activity of nonspecific T suppressors, to the influence of the factor of necrosis of alpha-tumor and alpha- and beta-interferons on B lymphocyte proliferation, and to the effects of synovial exudate from seropositive and seronegative patients. Demonstrate the results of integral estimation of the disorders of several characteristics of the immune system in RA patients with the use of the image recognition program. It is concluded that the clinical polymorphism of RA is specified by the pathogenetic heterogeneity of the disease based on varieties of combined normal and altered functions of different components of the immune system.

[Characteristics of secondary immunodeficiency in patients with neurocirculatory dystonia]. / Kharakteristika vtorichnogo immunodefitsita u bol'nykh tsirkuliatornoi distoniei.

AIM: Investigation of clinical-laboratory parameters of secondary immunodeficiency (SID) in patients with neurocirculatory dystonia (NSD). MATERIALS AND METHODS: Vegetative and immunological statuses were assessed in 104 males aged 30 to 57 years with NSD exposed to 0.01-0.1 Gy radiation after the Chernobyl accident. RESULTS: The patients were diagnosed to have SID the types and forms of which differed with NSD type. Symptoms of SID were evident in 29, 18, 13 and 83% of patients with mixed, hypotonic, hypertonic NSD, NSD without somatic disorders, respectively. CONCLUSION: As 85% of the examinees had SID, it is necessary to treat NSD with immunomodulation adjusted to each NSD type.

[Nerve regulation of the heart rhythm in patients with chronic inflammation]. / Izuchenie nervnoi reguliatsii serdechnogo ritma u bol'nykh s khronicheskim vospaleniem.

AIM: To study nervous regulation of cardiac rate variability (CRV) in patients with chronic inflammation (CI). MATERIAL AND METHODS: The computer version of CRV assessment was used in the study of 79 CI patients and 40 healthy controls. RESULTS: Nervous regulation of cardiac rhythm in CI patients at rest is characterized with imbalance of autonomic nervous system functions: potent sympathetic effects and weak parasympathetic effects in patients with herpes simplex virus infection; stability of parasympathetic influences with sympathetic variability in patients with chronic bronchitis. Using the emotional and physical tests it was found that there is a deficiency of sympathetic effects in patients with chronic bronchitis and parasympathetic dysfunction in patients with HSV infection. CONCLUSION: It is thought valid to include vegetotropic drugs in therapy of patients with chronic inflammation.

[Nerve regulation of cardiac rhythm in rheumatoid arthritis and multiple sclerosis patients]. / Izuchenie nervnoi reguliatsii serdechnogo ritma u bol'nykh revmatoidnym artritom i rasseiannym sklerozom.

AIM: To study nervous regulation of cardiac rhythm (CR) in patients with rheumatoid arthritis (RA) and multiple sclerosis (MS). MATERIAL AND METHODS: Nervous regulation of cardiac rhythm was studied in 57 patients with RA and MS vs 40 healthy subjects. RESULTS: It was found that nervous regulation of CR in RA and MS patients at rest is characterized by imbalance of functions of the autonomic nervous system with enhancement of ergotropic effects in patients with RA and deficiency of trophotropic impacts in growing ergotropic component in patients with MS. Stress tests led to dysfunction of CR central regulation with disturbed activity of the subcortical nervous centers (SNC) and autonomic maintenance of the processes, were characterized in emotional stress by insufficient activity of SNC and enhancement of parasympathetic effects in RA patients, hyperactivation of SNC with intensification of sympathetic impacts in MS patients manifesting in destabilizing effect of the sympathetic nervous system in both groups of patients. CONCLUSION: The findings should be taken into consideration when vegetotropic drugs are used in the treatment of RA and MS patients.

[Changes in functional activity of blood neutrophils in pollenosis patients: effects of specific immunotherapy]. / Izmeneniia funktsional'nykh svoistv neitrofilov krovi u bol'nykh pollinozom i vliianie spetsificheskoi immunoterapii.

AIM: The study of effective and regulatory functions of neutrophilic granulocytes in patients with pollenosis exacerbation, correction of the impaired neutrophil function with standard treatment and specific immunotherapy (SIT). MATERIALS AND METHODS: The study included 103 healthy donors (controls) and 122 patients with pollenosis aggravation. 69 of the latter received symptomatic treatment. 53 patients received preseasonal SIT with water-salt extracts of the pollen allergens. RESULTS: The untreated pollenosis patients had hyperproduction of interleukin-1 (IL-1) by nonstimulated blood neutrophils associated with elevation of NBT-reduction and lowering of phagocytic activity in decreasing count of Fc- and Ca-receptors. Effective SIT produced recovery of phagocytic activity, the number of Fc- and Ca-receptors, IL-1-activity of cell supernatants. CONCLUSION: One of the SIT targets in pollenosis patients is neutrophilic granulocytes.

[Immune status of patients with chronic bronchitis and neurocirculatory asthenia]. / Osobennosti immunnogo statusa bol'nykh khronicheskim bronkhitom s priznakami sindroma vegetativnoi distonii.

AIM: To study changes in immune system of patients with various forms of chronic bronchitis (CB) and neurocirculatory asthenia (NCA). MATERIAL AND METHODS: Neurological and immunological examinations were made in 84 patients with CB exacerbation and 51 control subjects. RESULTS: It was found that 60% of CB patients had NCA. No negative effects of NCA on immune system in CB patients were registered. Suppression of immune system and secondary immunodeficiency occurred more frequently in CB patients without signs of NCA. 40% of CB patients had vagotonic NCA in which immunological disorders manifested most clearly. CONCLUSION: Vegetative disorders in CB patients do not affect immunological system. Functional testing of autonomic nervous system is suggested for prediction of immune system condition.

[Study of the changes in the expression of histocompatibility antigens on the monocyte surface in the evaluation of the macrophage component of the immune system in rheumatoid arthritis]. / Izmeneniia ékspressii antigenov gistosovmestimosti na poverkhnosti monotsitov pri otsenke sostoianiia makrofagal'nogo zvena immunnoi sistemy pri revmatoidnom artrite.

Peripheral blood monocytes from 23 healthy persons and 25 RA patients were studied by cytohistochemistry, indirect immunofluorescence and cytophotometry to reveal interrelationship between cellular function of the system of mononuclear phagocytes and the expression of HLA-complex antigens in health and in RA. An increase in the phagocytic and metabolic activity of circulating monocytes was shown to be associated with a degree of the activity of an inflammatory process. A decrease in the level of the expression of HLA antigens class I was established in parallel with the rearrangement of the numerical ratio of cells expressing low and high levels of class II HLA-molecules. A degree of disorders of the expression of HLA-molecules and monocytic function was associated with a degree of RA activity.

[Seasonal changes of secondary immunodeficiency in patients with vascular dystonia]. / Sezonnye izmeneniia struktury vtorichnogo immunodefitsita u bol'nykh s vegetososudistoi distoniei.

The examination of 60 patients with vascular dystonia (VD) and immunological disorders shows that secondary immunodeficiency is not a stable condition. It is associated with seasons of the year and VD variants. Secondary immunodeficiency is more pronounced in winter. A correlation exists between mixed vegetative vascular dystonia and combined T-lymphocyte secondary immunodeficiency in winter. The findings may help in planning immunotherapy in "critical seasons" for patients with vegetative disorders.

[Clinical and immunological characteristics of primary and secondary antiphospholipid syndrome]. / Kliniko-immunologicheskaia kharakteristika pervichnogo i vtorichnovo antifosfolipidnogo sindroma.

A prospective study was made of 93 patients with antiphospholipid syndrome (APS), including 34 patients with primary APS (PAPS) and 59 with secondary APS (SAPS) associated with exanthematous lupus erythematosus (ELE). According to the clinical outcomes, PAPS is heterogeneous since the clinical and laboratory signs of ELE or lupus-like syndrome occurred in two thirds of the patients with PAPS. The clinical manifestations of PAPS and ELE-associated SAPS differed at the height of disease: the signs of vascular diseases were prevalent in patients with PAPS and ELE-associated systemic manifestations were predominant in those with SAPS. In the patients with APS who further developed ELE, unlike those with PAPS showed a high incidence of transient erythema and arthralgias. The levels of serological markers in patients with APS at its height did not differ. As compared with healthy individuals, patients with APS were found to have the similar changes in the nonspecific immunological parameters manifested by absolute lymphopenia, by the diminished Fc-phagocytosis of monocytes and neutrophils, by the elevated levels of circulating immune complexes, and by the high biocidal activity of neutrophils. There were no significant differences in the immunity of patients with PAPS and in those with SAPS.

[Normobaric hypoxy-therapy of patients with bronchial asthma]. / Normobaricheskaia gipoksiterapiia bol'nykh bronkhial'noi astmoi.

Conventional drug therapy for moderate atopic or mixed bronchial asthma was combined with normobaric hypoxytherapy (NBHT) in 32 patients (a course of 10 sessions) and was not combined in 20 control patients. Clinical results show that NBHT enhances response to conventional therapy of moderate bronchial asthma as confirmed by a significant relief of the clinical symptoms, by a significant rise of volumic and flow parameters of external respiration function, a fall in the number of CD 20+ B cells, low level of serum IgE, increased number of phagocyting neutrophils and cells carrying erythroblast antigen in peripheral blood.

[The efficacy of treating bronchial asthma patients at Khodzhaobigarm health resort]. / Effektivnost' lecheniia bol'nykh bronkhial'noi astmoi na kurorte Khodzhaobigarm.

A complex of therapeutic factors including mountain climate, pararadon procedures and measured muscular loads was used in 96 patients on treatment for bronchial asthma at Khodzhaobigarm health resort (1960 m above the sea level). As evident from clinicofunctional, allergological and immunological findings, the complex has a multifactor hyposensitizing and immunocorrective effect promoting normalization of bronchial receptor excitability, improvement of the lung mechanics and higher exercise tolerance.