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干扰素β治疗的多发性硬化症患者白细胞介素-2受体表达的时间进程

Time-course of interleukin-2 receptor expression in interferon beta-treated multiple sclerosis patients.

作者信息

Ferrarini A M, Sivieri S, Bulian P, Buttarello M, Biasi G, Tavolato B, Gallo P

机构信息

Department of Neurological and Psychiatrical Sciences, Second Neurological Clinic, University of Padova, Italy.

出版信息

J Neuroimmunol. 1998 Apr 15;84(2):213-7. doi: 10.1016/s0165-5728(97)00259-2.

Abstract

The time-course of CD25 (the 55-kD/alpha subunit of the interleukin-2 (IL-2) receptor) expression on CD4+ T lymphocytes, and serum levels of soluble IL-2 receptors (sIL-2R) and IL-2 were evaluated in relapsing-remitting multiple sclerosis (RRMS) patients treated with interferon beta-1b (IFNbeta1b). Peripheral blood samples were collected before therapy (T0), and 1 (T1), 2 (T2), 3 (T3), 6 (T4), and 12 (T5) months after therapy initiation. While at T1 and T2, half the patients showed an increased number of circulating CD4+ CD25+ lymphocytes and an up-regulation of CD25 expression, at T3 this T-cell subset was significantly reduced in all the patients. From T4 to T5, however, the progressive return to pretreatment values was observed. Serum sIL-2R levels were not significantly affected by IFNbeta1b at any time point. IL-2 was detected in only a few patients at T0, and never at T1 to T5. The transient up-regulation of CD25+ expression that occurred in about 50% of the patients may explain the unchanged relapse rate observed during the first 2 to 3 months after starting IFNbeta1b therapy. Our study demonstrates that IFNbeta1b down-regulates CD25 expression in vivo. This effect, however, was observed only after 3 months of therapy, and was followed by the return to pretreatment values after 6 to 12 months. Taken all together, our findings suggest that IFNbeta1b only transiently affects CD25 expression in vivo, and that this effect cannot account for the reported long-lasting beneficial action of IFNbeta1b on RRMS.

摘要

在接受β-1b干扰素(IFNβ1b)治疗的复发缓解型多发性硬化症(RRMS)患者中,评估了CD4⁺T淋巴细胞上CD25(白细胞介素-2(IL-2)受体的55-kD/α亚基)表达的时间进程,以及可溶性IL-2受体(sIL-2R)和IL-2的血清水平。在治疗前(T0)以及治疗开始后1(T1)、2(T2)、3(T3)、6(T4)和12(T5)个月采集外周血样本。虽然在T1和T2时,一半患者循环CD4⁺CD25⁺淋巴细胞数量增加且CD25表达上调,但在T3时所有患者的该T细胞亚群均显著减少。然而,从T4到T5,观察到其逐渐恢复至治疗前水平。在任何时间点,血清sIL-2R水平均未受到IFNβ1b的显著影响。仅在少数患者的T0时检测到IL-2,而在T1至T5时均未检测到。约50%的患者出现的CD25⁺表达的短暂上调可能解释了在开始IFNβ1b治疗后的前2至3个月观察到的复发率未变的现象。我们的研究表明,IFNβ1b在体内下调CD25表达。然而,这种效应仅在治疗3个月后观察到,随后在6至12个月后恢复至治疗前水平。综上所述,我们的研究结果表明,IFNβ1b仅在体内短暂影响CD25表达,且这种效应无法解释IFNβ1b对RRMS所报道的长期有益作用。

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