ГБОУ ВПО «Владивостокский государственный медицинский университет министерства здравоохранения и социального развития» Кафедра иностранных языков Факультет второго высшего и дополнительного образования «Sympathoadrenal system and parasympathetic nervous system role in the pathogenesis of rheumatoid arthritis» Студент: 301 группа, ф-т ВВ и ДО Курпатов И. Г. Научный руководитель: старший преподаватель кафедры иностранных языков Огородникова Э.Ю. Рецензент: зав. кафедрой факультетской терапии, д.м.н., проф. Дубиков А. И. Владивосток 2012

The rheumatoid arthritis is autoimmune disease which is characterized by chronic erosive arthritis (destruction of articular cartilage) or synovitis and systemic inflammation in organs of the body.

The rheumatoid arthritis: is not only a medical but great social problem; according to the international statistics steady rise of the rheumatoid arthritis incidence is observed all over the world; the rheumatoid arthritis is the most widespread autoimmune arthropathy.

is a great social problem not only because of the high incidence, but due to material damage of the society; since 2002 death rate of the rheumatoid arthritis has doubled; these data confirm the rheumatoid arthritis to become «threatened with death» disease.

It is noticeable that according to the international statistics the incidence of the rheumatoid arthritis is 0,5 – 1,5 %. Moreover, according to the official statistics in 2002 there were approximately 280 thousand rheumatoid arthritis patients.

The aim of the work is to study the influence of sympathoadrenal system and parasympathetic nervous system on the pathogenesis of autoimmune inflammation and thereby to identify brand-new therapeutical targets and proper methods of treatment.

The object of the study is to identify expression of α7 subunit of nicotinic acetylcholine receptors expressed on the surface of mast cells and its role in the pathogenesis of the rheumatoid arthritis autoimmune inflammation.

α7 subunit of nicotinic acetylcholine receptors expression, quantity and function of mast cells will beassessed by immunohistochemical, polymerase chain reaction and flow cytometry methods.

As a goals for the first stage of the study, data from novel articles and literature reviews devoted to following subjects have been analysed: 1. The main factors of the rheumatoid arthritis pathogenesis; 2. The main neuroimmune interaction mechanisms; 3. The main mechanisms of neuroimmune control under peripheral inflammation; 4. Mast cells roles in the pathogenesis of autoimmune arthropathy; 5. The role of α7 subunit of nicotinic acetylcholine receptors in autoimmune inflammation development of the rheumatoid arthritis pathogenesis.

The etiology of rheumatoid arthritis is still unknown. Furthermore, all the mechanisms of the rheumatoid arthritis pathogenesis are not completely comprehended. Therefore, in the first part of my work the main factors of the rheumatoid arthritis pathogenesis have been analysed.

Being one of the most prospective, notions about reciprocal action of nervous and immune system are developed. Mechanisms by means of which the central nervous system can influence on the immune response and can signal the immune system to modulate its function have been identified since last 20 years. Therefore, in the second part of my work the main neuroimmune interaction mechanisms have been analysed.

Significant achievements in study of immune- associated mechanisms in pathogenesis of different inflammatory diseases have ensured effective development of therapeutical targets and proper methods of treatment. However, the data on the mechanisms of disturbances in neuroimmune interactions, being one of the leading factor in pathogenesis of immune inflammation, have been scanty. Therefore, in the third part of my work the main mechanisms of neuroimmune control under peripheral inflammation have been analysed.

Mast cells play the crucial role in pathogenesis of rheumatoid arthritis autoimmune inflammation. It is noticeable, that mast cells granules contain substances with both proinflammatory and anti- inflammatory characteristics. Mast cell influence on metabolic process is key factor of different adaptative and pathological processes. Mast cells amount and activity in the synovial membrane of patients with rheumatoid arthritis and without inflammatory autoimmune diseases has been revealed to be different. Therefore, in the fourth part of my work mast cells roles in the pathogenesis of autoimmune arthropathy have been analysed.

Having an anti-inflammatory effect, the vagus nerve plays an important role in limiting the inflammatory process. This mechanism is realized by means of the nicotinic receptors composed of the α7 subunit. Therefore, α7 subunit of nicotinic acetylcholine receptors role in autoimmune inflammation development of the rheumatoid arthritis pathogenesis have been analysed.

Conclusion I.Systemic autoimmune inflammation located in the synovial membrane is the leading factor in the pathogenesis of the rheumatoid arthritis. In the rheumatoid arthritis Th 1 -type of T-cell immune response prevails. Predominance of the release of such proinflammatory cytokines as tumor necrosis factor α, interleukin-1 and interleukin-6, which play important role in joint destruction, over the antiinflammatory cytokines release is typical for Th 1 -type.

II.The convincing evidence that genetically determined program of inflammation development is existing was obtained. The information about this process is stored in the segmental neurons of the spinal cord. However, findings of recent studies confirm such a nonspecific defence reaction of the immune system as inflammation to be under control of nervous system, especially under control of its segmental division.

III. Peripheral inflammation hypothalamic-pituitary axis autonomic nervous system pro- and antiinflammatory actions The vagus nerve plays an important role in limiting the inflammatory response. Serum acetylcholinesterase also suppresses inflammation by boosting acetylcholine concentration. The sympathetic nervous system can exhibit both pro- and antiinflammatory actions.

Mast cell influence is a key factor of different adaptative and pathological processes. As universal immune cells, mast cells interact with many cells types and modulate their function. Mast cell was also proved to interact with such a resident central nervous system cell as astrocyte

IV. Mast cells have potential to affect pathogenesis of such diseases as diabetes mellitus and bullous pemphigoid in a variety of ways. Mast cells play a critical role in multiple sclerosis pathogenesis. Synovial mast cells play the crucial role in pathogenesis of the rheumatoid arthritis autoimmune inflammation.

V.α7 subunit of nicotinic acetylcholine receptors expressed by various immune cells, including mast cells plays the crucial role in antiinflammatory action of vagus nerve. In collagen-induced arthritis (experimental model of the rheumatoid arthritis), treatment with specific agonists of these receptors decreases activity of joint inflammation process.

Specific agonists of α7 subunit of nicotinic acetylcholine receptors may be better candidate for development as a novel therapeutic approach for the rheumatoid arthritis treatment. Development of agonists that do not cross the blood–brain barrier would improve the application of these kinds of agents for the treatment of chronic inflammatory diseases like the rheumatoid arthritis.