Blauvelt Andrew, Lebwohl Mark G, Bissonnette Robert
Department of Dermatology, Oregon Medical Research Center, Portland, Oregon, USA.
Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
J Invest Dermatol. 2015 Aug;135(8):1946-1953. doi: 10.1038/jid.2015.144. Epub 2015 Mar 24.
Biologics that neutralize specific cytokines have improved outcomes for several immune-mediated disorders but may also increase risks for particular side effects. This article postulates potential immunologic consequences of inhibiting components of the IL-23/T-helper cell 17 pathway-the target of next-generation biologics for treating psoriasis-based on clinical phenotypes of inherent or acquired deficiencies in this pathway. Generally, downstream deficiencies (e.g., IL-17A, IL-17F) are associated with fewer disorders compared with upstream deficiencies, suggesting that selectively blocking downstream targets may result in a narrower range of side effects. However, safety of these specific inhibitions must be established in long-term studies.
中和特定细胞因子的生物制剂改善了几种免疫介导疾病的治疗效果，但也可能增加特定副作用的风险。本文基于白细胞介素-23/辅助性T细胞17通路（治疗银屑病的新一代生物制剂的靶点）内在或后天缺陷的临床表型，推测抑制该通路成分的潜在免疫后果。一般来说，与上游缺陷相比，下游缺陷（如白细胞介素-17A、白细胞介素-17F）相关的疾病较少，这表明选择性阻断下游靶点可能会减少副作用的范围。然而，这些特异性抑制的安全性必须通过长期研究来确定。
