mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2018-4-577-588mimmun-1566Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESИНТРАНАЗАЛЬНЫЕ ИНГАЛЯЦИИ БИОАКТИВНЫХ ФАКТОРОВ, ПРОДУЦИРУЕМЫХ М2-МАКРОФАГАМИ, В ЛЕЧЕНИИ БОЛЬНЫХ С ОРГАНИЧЕСКИМИ ПОРАЖЕНИЯМИ ГОЛОВНОГО МОЗГАINTRANASAL INHALATIONS OF BIOACTIVE FACTORS PRODUCED BY M2 MACROPHAGES IN THE TREATMENT OF PATIENTS WITH ORGANIC BRAIN SYNDROMEОстанинА. А.OstaninA. A.

д.м.н., профессор, главный научный сотрудник, лаборатория клеточной иммунотерапии,

630099, г. Новосибирск, ул. Ядринцевская, 14,

ct_lab@mail.ru

PhD, MD (Medicine), Professor, Main Research Associate, Laboratory of Cellular Immunotherapy,

630099, Novosibirsk, Yadrintsevskaya str., 14

ostanin62@mail.ruДавыдоваМ. Н.DavydovaM. N.

врач-невролог клиники иммунопатологии,

г. Новосибирск

Neurologist, Clinic of Immunopathology,

Novosibirsk

СтаростинаН. М.StarostinaN. M.

к.м.н., заслуженный врач РФ, заведующая отделением иммунологии клиники иммунопатологии,

г. Новосибирск

PhD (Medicine), Honored Doctor of Russian Federation, Head, Immunology Department, Clinic of Immunopathology,

Novosibirsk

СахноЛ. В.SakhnoL. V.

к.б.н., старший научный сотрудник, лаборатория клеточной иммунотерапии,

г. Новосибирск

PhD (Biology), Senior Research Associate, Laboratory of Cellular Immunotherapy,

Novosibirsk

ШевелаЕ. Я.ShevelaE. Ya.

д.м.н., ведущий научный сотрудник, лаборатория клеточной иммунотерапии,

г. Новосибирск

PhD, MD (Medicine), Leading Research Associate, Laboratory of Cellular Immunotherapy,

Novosibirsk

ЧерныхЕ. Р.ChernykhE. R.

д.м.н., профессор, член-корр. РАН, заведующая лабораторией клеточной иммунотерапии,

г. Новосибирск

PhD, MD (Medicine), Professor, Corresponding Member, Russian Academy of Sciences, Head, Laboratory of Cellular Immunotherapy,

Novosibirsk

ФГБНУ «Научно-исследовательский институт фундаментальной и клинической иммунологии»РоссияResearch Institute of Fundamental and Clinical ImmunologyRussian Federation201825062018204577588Copyright © Останин А.А., Давыдова М.Н., Старостина Н.М., Сахно Л.В., Шевела Е.Я., Черных Е.Р., 20182018Останин А.А., Давыдова М.Н., Старостина Н.М., Сахно Л.В., Шевела Е.Я., Черных Е.Р.Ostanin A.A., Davydova M.N., Starostina N.M., Sakhno L.V., Shevela E.Y., Chernykh E.R.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/1566

Цель исследования – оценить безопасность и клиническую эффективность ингаляционной иммунотерапии на основе интраназального введения биоактивных факторов, продуцируемых М2-макрофагами, при лечении пациентов с органическими поражениями головного мозга (ОПМ).

В исследование, которое проводили по протоколу NCT02957123 (www.ClinicalTrails.gov), были включены 30 больных (10 мужчин и 20 женщин в возрасте от 18 до 81; Ме 62,5 лет) с ОПМ различного генеза. Оценку неврологического статуса и уровня 32 цитокинов в сыворотке крови больных проводили до начала курса ингаляционной иммунотерапии и через 2-3 дня после его завершения.

Курсовое лечение с использованием интраназальных ингаляций кондиционных сред М2- макрофагов (по 2 мл 1 раз в сутки в течение 28-30 дней) было безопасным и хорошо переносимым. Ни у одного из 30 пролеченных больных не было отмечено тяжелых нежелательных явлений и выраженных побочных реакций. Проведение ингаляционной иммунотерапии уже через 1 мес. после начала лечения сопровождалось положительной динамикой показателей неврологического статуса. При этом у 67% (20/30) больных регистрировался выраженный клинический ответ, который проявлялся коррекцией по всем используемым шкалам и вопросникам. Достигнутый эффект сохранялся также и через 6 мес. наблюдения. У остальных пациентов (33%, 10/30) отмечался умеренный клинический ответ в виде коррекции баллов по отдельным шкалам. В целом по группе пролеченных больных (n = 30) отмечалось: 1) снижение на 43% уровня тревоги и депрессии (по шкале HADS, pU=0,0008); 2) увеличение на 25% общей двигательной активности (устойчивости и походки, pU = 0,0001); 3) коррекция когнитивных функций (МоСа тест, pU = 0,007); 4) сокращение количества и уменьшение интенсивности симптомов болезни на 52% (pU = 0,0001). Установлено, что развитие выраженного клинического ответа на проводимую иммунотерапию сопряжено с коррекцией/нормализацией уровня фактора роста гепатоцитов (HGF) в сыворотке крови.

Ингаляционная иммунотерапия на основе интраназального введения биоактивных факторов, продуцируемых М2-макрофагами, позволяет повысить эффективность неврологического и функционального восстановления больных с органическими поражениями головного мозга. 

The aim of present study was to evaluate safety and clinical efficacy of inhalatory immunotherapy based on intranasal delivery of bioactive factors produced by M2 macrophages applied for treatment of patients with organic brain syndrome (OBS).

Materials and methods

Materials and methods. The study under the NCT02957123 protocol (www.ClinicalTrails.gov) included thirty patients with OBS of various genesis (10 men and 20 women aged 18 to 81; Me, 62.5 years). Neurological assessment and the levels of 32 cytokines in the blood serum of patients were evaluated before and 2-3 days after completion of inhalation immunotherapy.

Intranasal inhalations of cell-free culture medium of M2 macrophages (2 mL, once a day for 28-30 days) were safe and well tolerated. None of 30 treated patients had severe adverse events and serious treatmentrelated side reactions. One month after starting the inhalations, a positive dynamics in neurological status was noted in all the patients. A marked clinical response was documented in twenty out of thirty patients (67%), which manifested as improvement, according to all scales and questionnaires. The neurological improvement was not reversed over 6 months of follow-up period. In other ten patients (33%), a moderate clinical response was shown as improvement of individual scores. The positive changes were as follows: 1) a 43% decrease in anxiety and depression scores (according to HADS scale, pU = 0.0008); 2) an increase of total motor activity (stability and gait) by 25%, pU = 0.0001); 3) correction of cognitive functions (MoCa test, pU = 0.007); 4) reduced number and intensity of the disease symptoms by 52% (pU = 0.0001). This marked clinical response to immunotherapy is shown to be associated with correction/normalization of serum hepatocyte growth factor (HGF) level.

Conclusion

Conclusion. Inhalation immunotherapy based on intranasal delivery of bioactive factors produced by M2 macrophages can improve neurological and functional recovery in patients with organic brain syndrome. 

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The authors declare that there are no conflicts of interest present.