mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2006-4-539-546mimmun-490Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESЦИТОКИНОВЫЙ ПРОФИЛЬ У БОЛЬНЫХ ХРОНИЧЕСКИМИ ВИРУСНЫМИ ГЕПАТИТАМИ С ФИБРОЗОМ И ЦИРРОЗОМ ПЕЧЕНИCYTOKINE PROFILE IN PATIENTS WITH CHRONIC VIRUS HEPATITIS COMPLICATED WITH FIBROSIS AND CIRRHOSISЧерныхЕ. Р.ChernykhE. R.

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ct-lab@mail.ruСтаростинаН. М.StarostinaN. M.ct-lab@mail.ruЛеплинаО. Ю.LeplinaO. Yu.ct-lab@mail.ruШевелаЕ. Я.ShevelaE. Ya.ct-lab@mail.ruАгапитоваС. В.AgapitovaS. V.ct-lab@mail.ruШипуновМ. В.ShipunovM. V.ct-lab@mail.ruОстанинА. А.OstaninA. A.ct-lab@mail.ruКозловВ. А.KozlovV. A.ct-lab@mail.ruГУ НИИ клинической иммунологии СО РАМН, НовосибирскRussian Federation20062207201484539546Copyright © Черных Е.Р., Старостина Н.М., Леплина О.Ю., Шевела Е.Я., Агапитова С.В., Шипунов М.В., Останин А.А., Козлов В.А., 20142014Черных Е.Р., Старостина Н.М., Леплина О.Ю., Шевела Е.Я., Агапитова С.В., Шипунов М.В., Останин А.А., Козлов В.А.Chernykh E.R., Starostina N.M., Leplina O.Y., Shevela E.Y., Agapitova S.V., Shipunov M.V., Ostanin A.A., Kozlov V.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/490

Резюме. В работе проведен сравнительный анализ спонтанной и LPS-стимулированной продукции цитокинов, характеризующих баланс Th1/Th2 (IFN-γ/IL-4, IL-13), а также про- и противовоспалительную активность моноцитов (TNF-α/IL-10) в культурах клеток крови здоровых доноров и больных хроническими вирусными гепатитами с наличием фиброза и цирроза печени. Показано, что клетки периферической крови обследованных больных характеризуются выраженным усилением цитокин-продуцирующей функции, что проявляется высоким уровнем спонтанной и индуцированной продукции как Th1/провоспалительных, так и Th2/противовоспалительных цитокинов. При этом трансформация в цирроз связана с усилением спонтанной продукции IL-4 и IL-13 и прогрессирующим возрастанием спонтанной продукции IFN-γ, TNF-α и IL-10. В свою очередь утяжеление цирроза ассоциируется с нарастанием выраженности воспалительной активности крови и снижении противовоспалительного потенциала. Так, больные с циррозом печени класса С характеризуются значительно более высокими индексами соотношения TNF-α/IL-10 и IFN-γ/IL-10, чем больные с циррозом класса А. Кроме того была выявлена прямая взаимосвязь индекса TNF-α/IL-10 с интенсивностью цитолиза и тяжестью цирроза (баллом по Child-Pugh) и обратная связь между тяжестью цирроза и индексом LPS-стимуляции IL-10. Доминирование провоспалительных цитокинов, проявляющееся в увеличении индекса соотношения IFN-γ/IL-10 ассоциировано также с наличием анемии. Таким образом, особенности продукции цитокинов клетками крови при хронической вирусной инфекции у больных с фиброзом и циррозом печени отражают характер клинического течения заболевания.

Abstract. In present study, a comparative analysis of spontaneous and LPS-stimulated production of Th1/ Th2 (IFN-γ/IL-4, IL-13), and monocyte-derived pro- and anti-inflammatory cytokines (TNF-α/IL-10) was carried out in blood cell cultures of healthy donors and the patients with chronic viral hepatitis complicated with liver fibrosis and cirrhosis. The patients’ cells exhibited an increased production of both Th1/proinflammatory and Th2/anti-inflammatory cytokines. Meanwhile, hepatitis-induced cirrhotic transformation correlates with enhancement of spontaneous IL-4 and IL-13 production (not observed in fibrosis patients), and progressive increase of spontaneous IFN-γ, TNF-α and IL-10 secretion. In turn, the progression of cirrhosis is connected with increase of pro-inflammatory blood activity and reduction of anti-inflammatory potential. E.g., the patients with grade C cirrhosis have significantly higher index of TNF-α/IL-10 and IFN-γ/IL-10 ratio, as compared to the grade A patients. Moreover, we revealed a positive correlation of TNF-α/IL-10 ratio with cytolysis and severity of cirrhosis (Child-Pugh score), and a reverse correlation between the grade of liver cirrhosis and LPS-induced stimulation index of IL-10. Predominance of pro-inflammatory cytokines, displayed as increased IFN-γ/IL-10 ratio, was also associated with presence of anemia. Hence, the profile of cytokines produced by peripheral blood cells reflects some clinical features in the patients with chronic virus hepatitis complicated with fibrosis and cirrhosis.

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