Brod Staley A, Bauer Victoria L
Department of Neurology, University of Texas-Houston, Health Science Center, 6431 Fannin St, Houston, TX 77030, United States.
Department of Neurology, University of Texas-Houston, Health Science Center, 6431 Fannin St, Houston, TX 77030, United States.
Cytokine. 2014 Aug;68(2):86-93. doi: 10.1016/j.cyto.2014.04.003. Epub 2014 May 4.
Blocking the activity of IL-6 can inhibit autoimmune diseases such as rheumatoid arthritis and Crohn's disease.
We examined whether an antibody against IL-6, tocilizumab (TCZ) (Actemra®), used clinically in rheumatoid arthritis (RA) would have similar anti-inflammatory effects in EAE after oral administration.
DESIGN/METHOD: B6 mice were immunized with MOG peptide 35-55 and gavaged with control saline or TCZ during ongoing disease. Splenocytes, CD4(+) T cells or macrophages/monocyte lineage cells (CD11b(+)) from control fed or TCZ fed mice were adoptively transferred into active MOG peptide 35-55 immunized recipient mice during ongoing disease. Actively fed and recipient mice were examined for disease inhibition, inflammation, and cytokine responses.
Ingested (oral) TCZ inhibited ongoing disease and decreased inflammation. Adoptively transferred cells from TCZ fed donors protected against actively induced disease and decreased inflammation. There was a decrease in IL-6 in actively treated spleen, decrease in TNF-α, Th1-like cytokine IL-12 and increase in Th2-like cytokine IL-10 in active fed and adoptively treated recipients.
Ingested (orally administered) TCZ can inhibit disease, CNS inflammation, decrease pro-inflammatory Th1-like cytokines and increase Th2-like anti-inflammatory cytokines.
阻断白细胞介素-6（IL-6）的活性可抑制类风湿性关节炎和克罗恩病等自身免疫性疾病。
我们研究了临床上用于类风湿性关节炎（RA）的抗IL-6抗体托珠单抗（TCZ，商品名Actemra®）口服给药后在实验性自身免疫性脑脊髓炎（EAE）中是否具有类似的抗炎作用。
设计/方法：用髓鞘少突胶质细胞糖蛋白（MOG）肽35-55免疫B6小鼠，并在疾病进展期间给其灌胃对照生理盐水或TCZ。在疾病进展期间，将来自对照喂养或TCZ喂养小鼠的脾细胞、CD4(+) T细胞或巨噬细胞/单核细胞系细胞（CD11b(+)）过继转移到经MOG肽35-55主动免疫的受体小鼠中。对主动喂养的小鼠和受体小鼠进行疾病抑制、炎症和细胞因子反应检测。
摄入（口服）的TCZ可抑制疾病进展并减轻炎症。来自TCZ喂养供体的过继转移细胞可预防主动诱导的疾病并减轻炎症。在主动治疗的脾脏中IL-6减少，在主动喂养和过继治疗的受体中肿瘤坏死因子-α（TNF-α）、Th1样细胞因子IL-12减少，Th2样细胞因子IL-10增加。
摄入（口服）的TCZ可抑制疾病、中枢神经系统炎症，减少促炎性Th1样细胞因子并增加Th2样抗炎细胞因子。
