[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.

Circadian variations in immune values and serum melatonin in asthmatics.

Circadian variations in the immune status and serum melatonin were studied in asthmatics during exacerbation stage before and after treatment. Deviations from the normal (donor) immunogram values at 9.00 and 21.00 and decreased correlations between immune values and blood melatonin level were detected. The correlations of immune values between each other and with melatonin over the circadian cycle increased after treatment.

[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.

[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.

[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.

Circadian variations of melatonin concentration in saliva and blood content of immunocompetent cells in healthy individuals.

Salivary content of melatonin and parameters of the immune status were studied in young healthy individuals. Morning and evening levels of melatonin showed different correlations with some immunity parameters. It was assumed that the degree and type of correlation between the immune system and melatonin depend on the phase of circadian cycle, which should be considered during evaluation of immunoendocrine status.

[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.

[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.

[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.

[The immune status characteristics of patients with autonomic disorders]. / Kharakteristika immunnogo statusa u bol'nykh s vegetativnymi narusheniiami.

The state of immune system was examined in 133 patients with different clinical variants of vegetovascular dystonia (VVD). The following disorders were found: T-lymphopenia, increased concentrations of immunoglobulins A and M, elevated functional activity of monocytes in peripheral blood. The most pronounced T-lymphopenia was found in patients with vagoinsular form of VVD. The signs of secondary immunodeficiency were observed in patients with autonomic dysfunction. Their frequency and structure depended on the type and form of VVD. The most frequent laboratory signs of secondary immunodeficiency were registered in sympathoadrenal VVD form without clinical signs of somatic pathology.

[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.

[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.

[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.