Abstract
Traumatic brain injury (TBI) commonly proceeds as a severe disease with high morbidity that can lead to neurological disorders in some of these patients. TBI is associated by multidirectional abnormalities of immune system, which affect quantity and functions of T-, B-, and NK-lymphocytes leading to infectious complications or autosensibilization. Restoration of the disturbances in neuroimmune interactions after TBI may be achieved by means of immunomodulators that have neuroprotective properties and may potentially initiate regenerative CNS activity. IL-2 is a cytokine that possesses neurooperative and neuroprotective properties. In immune system, IL-2 is produced by T-cells in response to antigen stimuli; in CNS, by brain cells. Lack of IL-2 production by both T-lymphocytes and brain cells increases a possibility of autoimmune and inflammatory pathologies. The objective of present study was to evaluate possible effects of human recombinant IL-2 (rIL-2, Roncoleukin®, Biothech Ltd., Russia) upon state and correction of immune and neuro-endocrine TBI consequences. The study was performed in adult Wistar rats. Mechanical TBI was produced by the dropping load model. 72 hours after inflicting the TBI, r-IL-2, at dose 30 mg/kg was injected once a day for three times. The animals from control group received 0.15M NaCl solution over the same period. The results have shown that, within first hours and days after TBI, corticosterone levels showed a sharp increase, whereas testosterone concentrations were decreased.In parallel, an increase in cytotoxic and proliferative activity of splenocytes was revealed, as well as increased number of splenocytes at their late apoptotic stage. Three daily injections of rIL-2 resulted into a significant increase in corticosterone and testosterone levels in injured animals on the day 7 after TBI. The animals treated with rIL-2 have exhibited more rapid normalization of cytotoxic and proliferative activity of splenocytes and return to normal ratio of proliferating splenocytes vs. apoptotic cells. Therefore, usage of rIL-2 may correct neuro-endocrine and immune interaction disturbances after TBI and decrease risk of chronic neurological disorders in TBI patients.
Highlights
Иммуномодулирующее действие rIL-2 при Черепно-мозговая травма (ЧМТ) rIL-2 effects in traumatic brain injury ром врожденных адаптивных иммунных реакций и острой фазы воспаления являются кортикостероиды
Traumatic brain injury (TBI) commonly proceeds as a severe disease with high morbidity that can lead to neurological disorders in some of these patients
TBI is associated by multidirectional abnormalities of immune system, which affect quantity and functions of T, B, and NK-lymphocytes leading to infectious complications or autosensibilization
Summary
В иммунной системе на фоне ЧМТ развиваются разнонаправленные нарушения, затрагивающие содержание Т-, В- и NK-лимфоцитов, что приводит как к инфекционным осложнениям, так и аутосенсибилизации. Через 72 часа после нанесения ЧМТ крысам в течение 3-х дней один раз в сутки внутрибрюшинно вводили препарат rIL-2 в дозе 30 мг/кг. В работе показано, что в первые часы и сутки после нанесения ЧМТ в крови животных значительно повышается уровень кортикостерона и одновременно снижается концентрация тестостерона. В результате 3-дневного введения rIL-2 в дозе 30 мг/кг травмированным животным существенно повышает уровни кортикостерона и тестостерона на 7 сутки после ЧМТ. Медицинская Иммунология Medical Immunology (Russia)/Meditsinskaya Immunologiya тотоксической и пролиферативной активности спленоцитов и соотношения количества пролиферирующих спленоцитов к числу клеток, вошедших в апоптоз. Применение rIL-2 может скорректировать нарушение нейроэндокринных и иммунных дисфункций после ЧМТ и обеспечить снижение риска развития хронической неврологической патологии у больных ЧМТ. Ключевые слова: экспериментальная ЧМТ, rIL-2, кортикостерон, тестостерон, цитотоксичность, пролиферация лимфоцитов, апоптоз
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