Cytokine net role in mechanisms of neuroimmune interaction (literature review)

This work deals with the literature review on the problems associated with the progress of the national and foreign authors in studying the role of the cytokine net in the pathogenetic mechanisms of forming the diseases of the nervous system. Studying the peculiarities in the functions of a number of the immune system indices as the targets of the combined exposure to the production and other factors are known to be the actual aspect of the works analyzed in the recent years. A special attention in the literature studied is paid to the intersystem interactions between the nervous and the immune systems and. the immune systems and. the value of their homeostasis. The literature deals with the causes of the injuries and/or the cellular death of the nervous system and, as the consequence, the function changes of other organism systems and the production of their activity products. The change regularities in the pro-inflammatory cytokines (IL-1β, TNF-α, IL-6 and IL-12) in the diseases of different etiology including those which were stipulated by the factors of the production environment and other factors on the example of the multiple sclerosis as the neurodegenerative disease are represented in this paper. The possibilities of the disease objectify of the nervous system and the determination of their process severity in the clinical praxis based on the immunological indices and the patient complaints are given in this work. The studies testifying the different mechanisms of the autoimmune response realization in exposure to the neuro toxicant of different etiology are represented in this paper as well as the direct correlation between the antibody content to the proteins of the nervous tissue and the production of the pro-inflammatory cytokines has been revealed. At the same time, the common morpho-functional regularities of the changes in the central nervous system of the albino rats in the post-contact period as a result of the exposure to the metallic mercury vapors and. sublimate including the persons examined working at the production were indicated. In the conclusion. the important actuality role of the molecular-genetic studies dealing with the gene polymorphism of the cytokine net in the ethiopathogenesis of the autoimmune disease and. the problems of the early diagnostics of the neurodegenerative disorders in the employees exposed to the neurotoxicants of different chemical nature is indicated

Expression of CD25+ and CD95+ Surface Markers on Peripheral Blood Lymphocytes in Patients with Vibration Disease

Vibration disease occupies one of the leading places among occupational diseases. The development and course of vibration disease is accompanied by disorders in immune system.Aim of the study is to provide a comparative assessment of cells with markers of the early (CD25+) and late (CD95+) stage of lymphocyte activation and to compare them with the phenotypic composition of lymphocytes in patients with vibration disease.Materials and methods. The study includes men aged 36-60 years with vibration disease from exposure to local vibration (26 people) and from combined exposure to local and general vibration (28 people).Results. The most pronounced changes in the system of lymphocyte apoptosis are observed in patients with vibration disease from the combined effects of local and general vibration, manifested by the increase in the number of CD25+ and CD95+-lymphocytes. Increase of quantity of CD25+ at patients with a vibration disease from impact of local vibration and from the combined impact of local and general vibration is caused by increase in their number on lymphocytes what the direct correlation dependence between quantity of CD25+-lymphocytes and the number of CD3+, CD4+, CD8+, CD16+, CD20+-lymphocytes testifies to.Conclusions. In patients with vibration disease from the combined effects of local and general vibration, the increase in the number of CD95+ is due to an increase in their density on mature T-lymphocytes, as evidenced by the inverse relationship between the level of CD95+ and the CD3+-lymphocytes. The obtained data should be taken into account in order to develop new effective methods of prevention, treatment and prediction of the course of vibration pathology

REGULARITIES OF СOMPENSATORY-ADAPTIVE REACTIONS IMMUNE RESPONSE OF WORKERS IN CHRONIC EXPOSURE TO VINYL CHLORIDE

Laboratory and immunological study of male workers in the production of vinyl chloride was conducted. It has established that more pronounced stress of compensatory-adaptive reactions is observed in patients with incipient neurointoxication ("at risk”) in comparison to group of ‘healthy”. With increasing radiation exposure to vinyl chloride, duration (length of) exposure, as well as increasing the concentration of chloride in the blood, showed worsening of changes in the immune system of workers. Installed elevated levels of autoantibodies: the S-100, B-head. Ca-channel and the DNA appear to be indicative of early changes in certain structures of the nervous system. Some of the earliest and most sensitive indicators of the formation of body resistance to unfavorable working environment are: IgM, IL-1β, TNF-α, IL-8, autoantibodies to S-100, autoantibodies to the В-head. Ca-channel, autoantibodies to DNA

COMPARATIVE EVALUATION OF CYTOKINE PROFILE IN EXPERIMENTAL ANIMALS UNDER THE EFFECT OF PHYSICAL FACTORS (PRELIMINARY STUDY)

The results of studies of cytokine production in the serum of experimental animals exposed by general vibration and noise of industrial frequency. The aim of the work was comparative research of pro- and anti-inflammatory cytokines in animals under the effect of physical factors. 2 experiments of 4 series of studies within 15, 30, 60 and 120 days were conducted. Intact male albino rats were used as a control group. In all animals serum levels of cytokines IL-1β, IL-10, TNF-a (species-specific diagnostic kits Bender MedSystems (Austria)) were evaluated by ELISA. Mathematical processing of the results was carried out by methods of nonparametric statistics. Experiments on outbred albino rats determined both general patterns and features of the cytokine balance changes depending on the nature of the influence of physical factors in the dynamics of development of disorders in immune system. The decrease of IL-10 level under the influence of vibration is observed in 15 days and the one under the influence of noise is observed in 60 days. The decrease of IL-1β in rats is typical only at the effects of noise in 30 days and doesn't change at the effect of vibration. It was concluded that changes in the contents of cytokines in experimental animals under the effect of general vibration and noise production rate shows different mechanisms basic for the regulation of immune response

PECULIARITIES OF IMMUNOREACTIVITY OF ORGANISM OF EMPLOYEES WORKING IN CONDITIONS OF EXPOSURE OF NEUROTOXICANTS OF DIFFERENT CHEMICAL NATURE

The different forms and the degree of expression of the immune responses of the employees to the exposure to the neurotoxicants of different chemical nature (metallic mercury vapours, vinyl chloride and dichloroethane, epichlorohydrin and. allyl chloride), stipulated, mainly by the specific character of chemical factor, were revealed. The role of pro- and. anti-inflammatory cytokines in the immune regulation, processes was indicated to be in the exposure to the neurotoxicants. The pro- inflammatory trend, of the responses of different intensity without the dependence on the exposure factor was considered, as the common change regularity of the cytokine profile in the persons of the "risk group". The peculiarities of the immunoresponsiveness changes in dependence on the working period, duration (record of service) under the harmful working conditions displaying the different immune mechanisms in exposure to the harmful production, substances (metallic mercury vapours, vinyl chloride and. dichloroethane, epichlorohydrin. and. allyl chloride) were revealed

CHANGE OF REGULARITIES OF IMMUNE RESPONSE IN WORKERS EXPOSED TO METAL MERCURY VAPORS

The clinical-immunological examination of the employees working under conditions of the exposure to the metal mercury vapors has been performed. The change peculiarities of the immune responses have been revealed in the employees in dependence on the development stage of the neurointoxication with the metallic mercury vapors. The correlation between the changes of the individual immunological parameters associated with the dosed mercury load and its contents in the blood and urine has been indicated

Role of neurotropic antibodies in forming of neurological disorders in employees of chemical production

Using the neurospecific proteins as the markers of different pathological changes in CNS is known to be one of the perspective trends of the modern neurophysiology and medicine. That's why, this work aimed to reveal the change regularities in the antibody (AB) content to the neurospecific proteins in chronic exposure to the neurotoxicants of different chemical nature of employees. 170 workers males have been examined including 79 employees working at the production of vinyl chloride and exposed to vinyl chloride plus dichloroethane, as well as 81 males working at the production of caustic under conditions of the exposure to the metallic mercury vapours including . Measuring the autoantibody concentration to the myelin-associated glycoprotein (MGA) (AT to MAG) in the blood sera was performed using the standard hard-phasic immune-enzymic method by means of the test-system of the Company BUHLMANN (Sweden). As a result of studies it was foud that the increase in the AB concentration has been revealed in the healthy employees with a long-term working period and the persons with the initial manifestations of neurointoxication, working under conditions of the exposure to vinyl chloride and dichloroethane compared with the control group. The study results have allowed to reveal the increase in the AB levels to MAG in the employees with the initial manifestations of neurointoxication compared with the control group. It is worth to be noted that the AB concentration to MAG was significantly found to increase in the patients with chronic mercury intoxication compared to the healthy employees and the persons with the initial manifestations of neurointoxication. Thereto, it should be noted that the mean index values in the patients with CMI in the clinical picture in whom the asthenic disorders prevailed and in the patients with the prevalence of the cognitive disorders were significantly found to differ both between them and relatively to the persons with the initial manifestations of neurointoxication as well as the control group. Moreover, the higher AB levels have been revealed in the patients with the prevalence of the cognitive disorders compared with the patients with the prevalence of the asthenic disorders. The differences revealed in the intensity of the autoimmune responses in the employees induced by the exposure to mercury and vinyl chloride (more expressed in exposure to mercury) may possibly testify the different mechanisms based on the neurointoxication development. Determining the neuronal antibodies may serve not only as the diagnostic tool of the pathological process development in the nervous tissue but it may testify the need of performing the measures of prevention and rehabilitation of the employees exposed to the neurotoxicants

Studies of interrelations between neurotrophic antibodies and individual neurophysiological indices in patients with professional chronic mercury intoxication at the post-exposure period

Disturbances in the nervous system during chronic mercury intoxication (CМI) are accompanied by regular changes in the immune system. Diagnostic use of neurospecific protein markers of various pathological changes in the central nervous system is one of the promising areas of modern neuroimmunology. Prolonged exposure to the mercury vapors may cause disturbances of both CNS neurons and peripheral nerves. At the same time, the neuroimmune relationships underlying the evolving disease are not studied to sufficient grade, especially in the later post-contact period of chronic mercury intoxication. The aim of this work was to identify the relationship between the contents of antibodies to neurotrophic proteins of the nervous tissue, and changes of the neurophysiological indices characterizing the state of central and peripheral pathways in the nervous systems of the patients after chronic mercury intoxication (CMI). Our study immunological study included 30 males in the post-contact period of the CМI, who previously worked in contact with metallic mercury vapors. The clinical patterns of patients were dominated by encephalopathy, the main manifestation of which are mental disorders (more often in the form of organic asthenic disorder, or organic personality disorder with cognitive and emotional-volitional disorders of varying severity). The criteria for inclusion in the study were: verified diagnosis in all patients, written informed consent to participate in the study, a history of the harmful effects of metallic mercury vapor under production conditions. Statistical evaluation was carried out using Statistica for Windows 6.0 software. The levels of neurotrophic antibodies (AT), somatosensory evoked potentials (SSEP), electroneuromyography (ENMG) data were studied in terms of assessing the relationship between changes in specialized structures of the nervous tissue, and the state of the central and peripheral neural pathways in the patients after chronic mercury exposure. The following correlations were found: those between the concentrations of antibodies to endorphin p ф-END) and changes in central conducting structures, as well as between antibodies to proteins S-100, MBP, GFAP, NF-200, VG calcium channel, MAG, p-END, AH-R, Ser-R, M-OR and the speed of axonal impulse conduction within various peripheral neural structures. The interrelations revealed in this study indicate to pathological changes in specialized structures of the nervous tissue, which may be used as diagnostic indicators for clinical course of CМI in the post-contact period

CLINICAL VALUE OF REGULATORY AUTOANTIBODIES IN DEVELOPMENT OF NEUROINTOXICATION WITH METALLIC MERCURY VAPOURS

We studied the changes in content of the autoantibodies to the antigens from nervous tissue was performed in the employees contacting with, metallic mercury, in the patients with, the mercury intoxication, at the different stages of the pathological process. It was found that small increase of concentrations of the autoantibodies to the protein S-100 in the "practically" healthy employees may be considered, as the protective physiological mechanism.. Influence of the mercury on the employees' organisms promotes the change of autoimmune reactions that are characterized by the increase of content of antibodies to the brain-specific proteins in blood serum.. The decrease of the antibody levels in patients with chronic mercury intoxication, in remote period and the increase of severity of pathological process testifies to the dysregulation in the immune system.. It was determined, that the increase of autoantibodies to MAG was typical only for the patients with chronic mercury intoxication. (CMI), thereby, higher levels of autoantibodies were observed in the patients with more dominated cognitive disorders in comparison with the patients with more dominated asthenic disorders. In healthy employees and the ones of "risk group" concentrations of autoantibodies to MAG were at the level of control. Increased, levels of autoantibodies to MAG testify to the formation of neurodegenerative changes and. are one of the diagnostic criteria

Закономерности изменений иммуно-гормональной регуляции при вибрационной болезни и нейросенсорной тугоухости

The purpose of the research was to identify changes in immune and hormonal regulation in patients with hand-arm vibration syndrome and sensorineural hearing loss to substantiate informative biomarkers.Materials and methods. Men with occupational injury induced by exposure to vibration and noise were examined. The first group included 26 people diagnosed with stage 1 and 2 hand-arm vibration syndrome. The second group consisted of 38 patients diagnosed with sensorineural hearing loss. Serum levels of cortisol, dehydroepiandrosterone sulfate, prolactin, free triiodothyronine (T3), free thyroxine  (T4), thyroid-stimulating hormone (TSH), and interleukins IL-1β, IL-8, IL-10 were determined by enzyme-linked immunosorbent assay.Results. The results of the study revealed the peculiarities in the immune and hormonal regulation in hand-arm vibration syndrome and sensorineural hearing loss. More pronounced changes were observed in sensorineural hearing loss. A common pattern in patients with hand-arm vibration syndrome and sensorineural hearing loss was an increase in cortisol, prolactin and IL-8 and a decrease in free T4 and IL-1β. Differences in the identified changes in the immune and hormonal status were characterized by increased TSH production in the first group, and increased free T 3 production and decreased IL-10 in the second group. In hand-arm vibration syndrome, high levels of cortisol were accompanied by a decrease in the IL-1β and IL-10 concentrations. In sensorineural hearing loss, an increase in the prolactin concentration was accompanied by increased production of IL-8.Conclusions. The identified features of immune and hormonal relations may be induced by the intensity of cortisol and prolactin production under the effects of various physical factors. Persistent high levels of cortisol and prolactin in the examined patients are important pathogenetically significant factors in the development of the disease. New laboratory indicators (IL-4, prolactin, free T3) for additional diagnosis of occupational sensorineural hearing loss were identified.Цель исследования – выявить закономерности иммуно-гормональной регуляции при вибрационной болезни и нейросенсорной тугоухости для обоснования информативных биомаркеров.Материалы и методы. Проведено обследование мужчин с профессиональной патологией, индуцированной воздействием вибрации и шума. В первую группу включены 26 пациентов с вибрационной болезнью I–II стадии, во вторую – 38 пациентов с профессиональной нейросенсорной тугоухостью. Методом  иммуноферментного анализа в сыворотке крови определяли содержание кортизола, дегидроэпиандростерона сульфата, пролактина, свободного трийодтиронина, свободного тироксина,  тиреотропного гормона (ТТГ); интерлейкина (IL) 1β, IL-8, IL-10.Результаты. Результаты исследования позволили выявить особенности иммуно-гормональной регуляции при вибрационной болезни и нейросенсорной тугоухости. Общей закономерностью у пациентов с вибрационной болезнью и нейросенсорной тугоухостью являются возрастание кортизола, пролактина, IL-8 и снижение свободного (св.) Т4, IL-1β. Различия выявленных изменений в иммуно-гормональном статусе характеризовались для первых усилением продукции ТТГ, для вторых – возрастанием продукции св. Т3 и снижением IL-10. При вибрационной болезни высокие уровни кортизола сопровождались снижением концентрации IL-1β и IL-10, а при нейросенсорной тугоухости возрастание концентрации пролактина – увеличением продукции IL-8.Заключение. Выявленные особенности иммуно-гормональных взаимоотношений могут быть обусловлены  интенсивностью выработки кортизола и пролактина при воздействии физических факторов различной  природы. Сохраняющиеся высокие концентрации кортизола и пролактина у обследованных являются важными патогенетически значимыми факторами в развитии и течении заболеваний. Определены новые биомаркеры для дополнительной диагностики профессиональной нейросенсорной тугоухости (IL-4, пролактин, св. Т3).