Перспективы применения тоцилизумаба при системной склеродермии

Интерлейкин 6 (ИЛ6) – один из ключевых цитокинов, участвующих в процессе воспаления и обладающий плейотропными свойствами. Разнообразные эффекты ИЛ6 осуществляются в результате передачи внутриклеточного сигнала двумя путями – через прямое связывание с мембранным рецептором с молекулярной массой 80 кДa («классический» путь) или вследствие абсорбирования комплекса ИЛ6 с его растворимым рецептором на другом трансмембранном рецепторе – gp130 (транссигнализация). Разные пути сигнализации вызывают различные последствия. Классический путь передачи сигнала активирует преимущественно протективные и регенеративные процессы, транссигнализация несет провоспалительный потенциал. В обзоре приведены схемы реализации сигнальных стимулов и показано, что ИЛ6 и его рецепторы представляют собой динамическую систему со сложно организованной регуляцией, позволяющей адаптироваться к стрессовым изменениям гомеостаза. Детально рассмотрены данные, свидетельствующие о влиянии ИЛ6 на развитие и поддержание ряда характерных для системной склеродермии (ССД) патогенетических нарушений, таких как активация эндотелия, развитие и поддержание воспаления и избыточное отложение компонентов экстрацеллюлярного матрикса в тканях. Активация эндотелиальных клеток в процессе транссигнализации приводит к усилению экспрессии молекул адгезии, высвобождению хемокинов и последующему выделению ИЛ6. Избыточная секреция ИЛ6 может инициировать фиброзирующий процесс и способствовать дальнейшему развитию патологических нарушений. При ССД имеют место аутоиммунные нарушения, теоретически связанные с гиперпродукцией ИЛ6. Повышение концентрации ИЛ6 в крови при ССД ассоциируется с клиническими параметрами заболевания – активностью, тяжестью, ухудшением прогноза и снижением выживаемости. В совокупности приведенные данные свидетельствуют о том, что блокирование ИЛ6 может иметь терапевтический потенциал при ССД. Приведены первые клинические данные об успешном применении блокатора рецепторов ИЛ6 тоцилизумаба для лечения ССД.

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