Ức chế Interleukin-6 trong quản lý viêm màng bồ đào không nhiễm trùng và những ứng dụng vượt xa

Journal of Ophthalmic Inflammation and Infection - 2019
Samendra Karkhur1, Murat Hasanreisoğlu1, Erin Vigil1, Muhammad Sohail Halim1, Muhammad Hassan1, Carlos Plaza1, Nam V. Nguyen1, Rubbia Afridi1, Anh Tran1, V. Diana1, Yasir J. Sepah1, Quan Dong Nguyen1
1Byers Eye Institute, Spencer Center for Vision Research, Stanford University, 2370 Watson Court, Suite 200, Palo Alto, CA, 94303, USA

Tóm tắt

Tóm tắtNền tảngViêm màng bồ đào bao gồm nhiều rối loạn viêm có đặc trưng bởi sự viêm mắt. Cơ chế bệnh lý tiềm ẩn bao gồm một sự tương tác phức tạp giữa nhiều con đường viêm. Interleukin-6 là một trung gian quan trọng của quá trình viêm trong viêm màng bồ đào và là trọng tâm nghiên cứu trong việc phát triển các liệu pháp sinh học mới trong việc quản lý viêm màng bồ đào không nhiễm trùng.Thân bàiViệc sử dụng steroid để ức chế toàn diện các con đường viêm thường là bước đầu tiên trong quản lý viêm màng bồ đào không nhiễm trùng cấp tính. Tuy nhiên, liệu pháp kéo dài với steroid liên quan đến những tác dụng phụ toàn thân và mắt, do đó cần phát triển các tác nhân thay thế steroid. IL-6 là một cytokine do nhiều tế bào miễn dịch sản xuất, để đáp ứng với các kiểu phân tử và ảnh hưởng đến nhiều tế bào viêm khác nhau. Đặc biệt, IL-6 tham gia vào sự phân hóa của tế bào CD-4 thành tế bào Th-17, đã được chứng minh đóng vai trò quan trọng trong các bệnh do miễn dịch như viêm màng bồ đào. Hoạt động điều chỉnh miễn dịch phổ quát này khiến IL-6 trở thành một mục tiêu tuyệt vời cho liệu pháp điều chỉnh miễn dịch. Tocilizumab là chất ức chế IL-6 đầu tiên cho thấy tác dụng hiệu quả trên con người. Nó ức chế IL-6 gắn vào cả thụ thể bám màng và tan trong dịch và có thể được sử dụng qua đường tĩnh mạch (IV) và dưới da (SC). Nó đã được FDA phê duyệt để điều trị viêm khớp dạng thấp (RA) và viêm khớp thiếu niên không rõ nguyên nhân (JIA). Sau khi được phê duyệt trong các bệnh toàn thân, hiệu quả của nó đã được chứng minh trong nhiều nghiên cứu viêm màng bồ đào, bao gồm một thử nghiệm lâm sàng giai đoạn 2 (STOP-Uveitis). Tổng thể, tocilizumab đã cho thấy một hồ sơ an toàn tốt với nguy cơ ung thư tương thích với dự đoán ở bệnh nhân viêm khớp dạng thấp. Tuy nhiên, liệu pháp tocilizumab đã được chứng minh làm tăng nguy cơ thủng tiêu hóa và giảm bạch cầu trung tính phụ thuộc liều. Sau thành công của tocilizumab, một số tác nhân khác nhắm vào con đường IL-6 đang trong quá trình nghiên cứu. Những tác nhân này bao gồm sirukumab, siltuximab, olokizumab, clazakizumab và EBI-031 nhắm vào IL-6; Sarilumab và ALX-0061 tác động lên thụ thể IL-6.Kết luậnCác nghiên cứu đã chứng minh rằng các chất ức chế IL-6 có thể hiệu quả trong việc quản lý viêm màng bồ đào không nhiễm trùng (NIU). Ngoài ra, mức độ IL-6 cũng tăng cao trong các bệnh lý mạch máu mắt khác như tắc tĩnh mạch võng mạc và phù hoàng điểm do tiểu đường. Vai trò của việc ức chế IL-6 có thể được mở rộng trong tương lai để bao gồm việc quản lý các bệnh lý mạch máu võng mạc và phù hoàng điểm không do viêm màng bồ đào.

Từ khóa


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