Nakajima Hideto, Hosokawa Takafumi, Doi Yoshimitu, Ikemoto Toshiyuki, Ishida Shimon, Kimura Fumiharu, Hanafusa Toshiaki
Division of Neurology, Department of Internal Medicine I, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Int J Mol Sci. 2012 Sep 25;13(10):12213-23. doi: 10.3390/ijms131012213.
A Japanese randomized controlled study showed that Interferon â (IFN-â1b) therapy is clinically effective in decreasing the frequency of attacks in multiple sclerosis (MS), even in optico-spinal MS (OSMS). However, recent studies have shown that IFN-â (IFN-â1a/IFN-â1b) treatment was not effective in neuromyelitis optica (NMO) patients and that the diminished benefit of IFN-â treatment in NMO may be due to different immune responses to IFN-â. We determined longitudinally the expression of CCR5, CXCR3 and CCR4 on CD4+ T and CD8+ T cells in the blood from patients with NMO and MS treated with IFN-â1b. During a 12-month period of IFN-â1b therapy, the annualized relapse rate decreased in MS patients but not in NMO patients. There was no significant difference in the expression of the chemokine receptors between NMO and MS at baseline. The percentages of CD4+CCR5+ and CD4+CXCR3+ T cells, representative of the Th1 response, were decreased in both NMO and MS after treatment. The percentage of CD4+CCR4+ T cells, representative of the Th2 response, was decreased in MS, but those for NMO was significantly increased compared with the pretreatment levels. Our results indicate that IFN-â1b-induced up-modulation of the Th2 response in NMO patients may be the source of differences in the therapeutic response to IFN-â1b therapy. In the present study, Th2 predominance is involved in the pathogenesis of NMO.
一项日本的随机对照研究表明,干扰素β(IFN-β1b)治疗在降低多发性硬化症(MS)发作频率方面具有临床疗效,即使在视神经脊髓型MS(OSMS)中也是如此。然而,最近的研究表明,IFN-β(IFN-β1a/IFN-β1b)治疗对视神经脊髓炎(NMO)患者无效,且IFN-β治疗在NMO中疗效降低可能是由于对IFN-β的免疫反应不同。我们纵向测定了接受IFN-β1b治疗的NMO和MS患者血液中CD4+T细胞和CD8+T细胞上CCR5、CXCR3和CCR4的表达。在为期12个月的IFN-β1b治疗期间,MS患者的年化复发率下降,但NMO患者未下降。基线时,NMO和MS之间趋化因子受体的表达无显著差异。治疗后,代表Th1反应的CD4+CCR5+和CD4+CXCR3+T细胞百分比在NMO和MS中均下降。代表Th2反应的CD4+CCR4+T细胞百分比在MS中下降,但NMO患者的该百分比与治疗前水平相比显著增加。我们的结果表明,IFN-β1b诱导的NMO患者Th2反应上调可能是对IFN-β1b治疗反应差异的来源。在本研究中,Th2优势参与了NMO的发病机制。