Роль интерлейкина 6 в развитии кардиоваскулярной патологии

Хотя роль воспаления в развитии атеросклеротического поражения сосудов как ведущей формы органной патологии при сердечно-сосудистых заболеваниях (ССЗ) обсуждается уже более 100 лет, только в течение последних 30 лет «воспалительная» теория атеросклероза стала рассматриваться как одно из важнейших направлений фундаментальных и клинических исследований в кардиологии и других разделах биологии и медицины. По современным представлениям, хроническое субклиническое (low grade) воспаление, развитие которого связывают с неконтролируемой активацией врожденного и приобретенного иммунитета, играет фундаментальную роль на всех стадиях прогрессирования атеросклеротического процесса, связанного с ССЗ. Фундаментальный вклад воспаления в развитие атеросклеротического поражения сосудов привлек внимание к схожести механизмов иммунопатогенеза атеросклероза при ССЗ и ревматоидного артрита, а в дальнейшем – и других системных иммуновоспалительных ревматических заболеваний (ИВРЗ). В спектре многочисленных медиаторов воспаления и «иммунных» клеток, участвующих в иммунопатогенезе атеросклероза как при ССЗ, так и при ИВРЗ, центральное место занимают такие «провоспалительные» цитокины, как интерлейкин (ИЛ) 1, ИЛ-6, фактор некроза опухоли α, а также ИЛ-17 и интерферон типа I, тесно взаимодействующие рамках «цитокиновой сети». В качестве перспективной терапевтической «мишени» особое внимание привлекает ИЛ-6, занимающий центральной место в развитии многих ИВРЗ, с одной стороны, и ССЗ, связанных с атеросклеротическим поражением сосудов (ишемическая болезни сердца, острый коронарный синдром, болезнь периферических артерий, ишемический инсульт, сердечная недостаточность и другие) – с другой. Особо важное значение имеет тот факт, что гиперпродукция ИЛ-6 играет важную роль в развитии широкого спектра кардиометаболических заболеваний, включая сахарный диабет 2-го типа, ожирение, хроническую болезнь почек, метаболически ассоциированной жировой болезни печени, ассоциирующихся с развитием атеросклеротического поражения сосудов. Получены данные, свидетельствующие о важном клиническом значения ИЛ-6 для прогнозирования риска преждевременной летальности и других сердечно-сосудистых осложнений как в общей популяции условно «здоровых» людей, так и у больных с различными проявлениями и формами ССЗ. В настоящее время разработано несколько генно-инженерных биологических препаратов, представляющих собой моноклональные антитела, специфичные в отношении как рецепторов ИЛ-6, так и самого ИЛ-6. Недавно инициировано несколько рандомизированных клинических исследований, посвященных изучению эффективности и безопасности новых моноклональных антител к ИЛ-6: зилтивекимаб (Ziltivekimab), клазакизумаб (Clazakizumab), Pacibekitug (TOUR006) у пациентов с ишемической болезнью сердца, сердечной недостаточностью, в том числе страдающих хронической болезнью почек. В статье будут рассмотрены новые данные, касающиеся патогенетического и клинического значения ИЛ-6, и перспективы ингибиции ИЛ-6 в качестве компонента противовоспалительной терапии ССЗ.

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