Saitoh Kodai, Kon Shigeyuki, Nakatsuru Takuya, Inui Kyosuke, Ihara Takeru, Matsumoto Naoki, Kitai Yuichi, Muromoto Ryuta, Matsuda Tadashi
Department of Immunology, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-0815, Japan.
Department of Molecular Immunology, Faculty of Pharmaceutical Sciences, Fukuyama University, Fukuyama 729-0292, Japan.
Biochem Biophys Rep. 2016 Aug 26;8:139-145. doi: 10.1016/j.bbrep.2016.08.021. eCollection 2016 Dec.
Cyclosporin A (CsA) is effective at reducing pathogenic immune responses, but upon withdrawal of CsA the immune response often "rebounds" resulting in a relapse or exacerbation of disease. The mechanisms, cells and cytokines involved in the relapse or exacerbation after CsA withdrawal are unknown. We hypothesized that CsA withdrawal induces IL-17 production that could be responsible for relapse, and examined the effect of anti-IL-17A antibody on relapse induced after CsA withdrawal in mouse experimental autoimmune encephalomyelitis (EAE). CsA treatment markedly decreased the EAE disease score during the first episode, but augmented disease severity after CsA withdrawal, compared to untreated mice. After discontinuation of CsA the production of IL-17A was increased and the severity of relapse in EAE was reduced by treatment with anti-IL-17A antibody. These results suggest that the resumption of T cell immune responses after CsA withdrawal leads to a burst of IL-17A production that is at least partially responsible for relapse in EAE mice.
环孢素A（CsA）在降低致病性免疫反应方面有效，但停用CsA后，免疫反应常常“反弹”，导致疾病复发或加重。CsA撤药后复发或病情加重所涉及的机制、细胞和细胞因子尚不清楚。我们推测，停用CsA会诱导IL-17产生，这可能是复发的原因，并研究了抗IL-17A抗体对小鼠实验性自身免疫性脑脊髓炎（EAE）中CsA撤药后诱导的复发的影响。与未治疗的小鼠相比，CsA治疗在首次发作期间显著降低了EAE疾病评分，但在停用CsA后增加了疾病严重程度。停用CsA后，IL-17A的产生增加，抗IL-17A抗体治疗降低了EAE复发的严重程度。这些结果表明，停用CsA后T细胞免疫反应的恢复导致IL-17A产生激增，这至少部分是EAE小鼠复发的原因。
