Инфекция и иммунитет. 2015; 5: 349-358
ЦИТОКИНЫ И ГЕРПЕСВИРУСЫ ПРИ РАССЕЯННОМ СКЛЕРОЗЕ У ДЕТЕЙ
https://doi.org/10.15789/2220-7619-2015-4-349-358Аннотация
Ранее установлено (Г.П. Иванова, 2012), что у подростков хроническое течение лейкоэнцефалита, обусловленное неадекватным ответом системы цитокинов на сочетание двух герпесвирусов (ГВ) — EBV и HHV-6, в 44% случаев приводит к развитию РС. Цель исследования состояла в характеристике ответа цитокинов у детей с РС с одновременным скринингом наличия у них активной ГВ-инфекции. Под наблюдением были 39 детей с диагнозом «РС»; из них 34 переносили рецидивирующий-ремиттирующий (РР) РС, а 5 имели прогрессирующее течение РС (ПРС). Концентрации цитокинов IL-1β, IL-6, IL-8, IL-10, IFNα, IFNγ и IL-4 определяли в сыворотке крови и цереброспинальной жидкости (ЦСЖ) методом ИФА, ДНК ГВ выявляли в ПЦР. Цитокиновый статус детей с РС имел отличия в зависимости от фазы болезни, клинической тяжести обострения и течения процесса. Период обострения РРРС ассоциирован с накоплением в крови IL-8, IL-10 и IL-6, модуляциями индекса IFNγ/IL-4 по мере роста клинической тяжести обострения. Тяжелое обострение болезни у детей с ПРС сопровождалось усилением системного ответа IL-8. ДНК герпесвирусов выявлена у 27 из 39 (69%) пациентов в крови и у 17 (44%) в ЦСЖ, с доминированием EBV (93%), часто в сочетании с HHV-6. В периоде обострения частота обнаружения ДНК ГВ нарастала в 2–3 раза по сравнению с периодом ремиссии. В отличие от детей с РРРС, у всех 5 пациентов с ПРС обнаружена микст-инфекция из 3–4 герпесвирусов. По совокупности результатов исследования можно заключить, что ГВ-инфекция играет важную роль в патогенезе РС у подростков, участвуя в обострении и прогрессии болезни путем воздействия на системный ответ цитокинов. Среди ГВ доминирует EBV-инфекция, однако риск развития РС резко нарастает при сочетании EBV с другим лимфотропным вирусом — HHV-6.
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Russian Journal of Infection and Immunity. 2015; 5: 349-358
CYTOKINES AND HERPESVIRUSES IN CHILDREN WITH MULTIPLE SCLEROSIS
https://doi.org/10.15789/2220-7619-2015-4-349-358Abstract
It was determined earlier (G.P. Ivanova, 2012) that a chronic course of leukoencephalitis in teenagers caused by inadequate response of cytokine system to the combination of two herpesviruses (HV) — EBV and HHV-6, leads to the development of multiple sclerosis (MS) in 44% of cases. The research objective was to characterize the cytokine response in children with MS with simultaneous screening of the presence of active HV infections. 39 children with the diagnosis “MS” were under observation, 34 of them had relapsing-remitting (RR) MS, and 5 children had a progressing course of MS (PMS). Concentration of cytokines IL-1β, IL-6, IL-8, IL-10, IFNα, IFNγ, and IL-4 was identified in blood serum and cerebrospinal liquid (CSF) by enzyme-linked immunosorbent assay, HV DNA was revealed by PCR. Cytokine status in children with MS had some differences depending on the phase of the disease, clinical severity of the relapse and the course of MS. The relapse phase of RRMS was associated with the accumulation of IL-8, IL-10, and IL-6 in the blood, and index IFNγ/IL-4 modulations in accordance with the clinical severity of the relapse. A severe aggravation of the disease in children with PMS was accompanied by the increase of IL-8 system response. HV DNA was revealed in 27 patients from 39 ones (69%) in blood and in 17 patients (44%) in CSF with the predominance of EBV (93%), frequently in combination with HHV-6. During an acute period the frequency of HV DNA identification increased 2–3 times to compare with the remission period. Unlike children with RRMS, a mixed-infection of 3–4 herpes viruses was revealed in all 5 patients with PMS. According to the results summary it is possible to make a conclusion that HV-infection has an important role in MS pathogenesis in teenagers, taking part in the aggravation and progression of the disease by its effect on the cytokine system response. EBV-infection dominates among HV, however the risk of MS development increases to a great extent in the case of EBV association with another lymphotropic virus — HHV-6.
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