Enhancement of Chemokine Expression by Interferon Beta Therapy in Patients With Multiple Sclerosis
Enhancement of Chemokine Expression by Interferon Beta Therapy in Patients With Multiple Sclerosis
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DOI：
10.1001/archneurol.2009.138
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发表时间：
2009-10-01
影响因子：
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通讯作者：
Hemmer, Bernhard
中科院分区：
文献类型：
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作者：
Cepok, Sabine;Schreiber, Herbert;Hemmer, Bernhard
背景：干扰素β已被批准用于多发性硬化症（MS）的治疗。人们认为干扰素β的免疫调节活性而不是抗病毒活性是疾病改善的原因。干扰素β对免疫细胞的化学吸引力的影响尚未得到充分解决。目的：探讨干扰素β对标准化环境下趋化因子及其受体表达的影响。设计：采用实时定量聚合酶链反应法测定新鲜血液中14种趋化因子及14种趋化因子受体基因的表达。地点：德国的门诊单位。患者：2006年8月24日至12月15日，未接受治疗和接受干扰素β治疗的中和抗体（nab）检测呈阳性和阴性的MS患者被招募为初始研究，2007年3月12日至2007年4月2日，被招募为验证研究。主要观察指标：基因表达和血清趋化因子蛋白水平。结果：CCL1、CCL2、CCL7、CXCL10、CXCL11、CCR1。在干扰素β治疗的nab阴性MS患者中，基因表达强烈上调。相比之下，干扰素β治疗的nab阳性MS患者的基因表达与未治疗的对照供体个体没有差异。抗体滴度与趋化因子和趋化因子受体基因表达呈负相关。因此，干扰素β治疗的nab阴性MS患者血清趋化因子蛋白水平显著高于未治疗或干扰素β治疗的nab阳性MS患者。结论：我们证明了干扰素β在外周免疫细胞中强烈上调一组趋化因子和CCR1。这些趋化因子的外周上调；可能减少免疫细胞对中枢神经系统的化学吸引力，从而增加干扰素的治疗效果。
Background: Interferon beta has been approved for the treatment of multiple sclerosis (MS). it is believed that immunomodulatory rather than antiviral activity of interferon beta is responsible for disease amelioration. The impact of interferon beta on the chemoattraction of immune cells has not been fully addressed.Objective: To address the influence of interferon beta on the expression of chemokines and their receptors in a standardized setting.Design: The expression of 14 chemokines and 14 chemokine receptor genes was determined by quantitative real-time polymerase chain reaction from fresh blood samples.Setting: Outpatient units in Germany.Patients: Untreated and interferon beta-treated patients with MS who tested positive and negative for neutralizing antibodies (NABs) were recruited from August 24, 2006, through December 15, 2006, for the initial study and from March 12, 2007, through April 2, 2007, for the validation study.Main Outcome Measures: Gene expression and serum chemokine protein levels.Results: CCL1, CCL2, CCL7, CXCL10, CXCL11, and CCR1. gene expression was strongly upregulated in interferon beta-treated, NAB-negative MS patients. In contrast, gene expression in interferon beta-treated, NAB-positive MS patients did not differ from untreated control donor individuals. Antibody titers inversely correlated with chemokine and chemokine receptor gene expression. Accordingly, serum chemokine protein levels of interferon beta-treated, NAB-negative MS patients were significantly higher than in untreated or interferon beta-treated, NAB-positive MS patients.Conclusions: We demonstrate that interferon beta strongly upregulates a set of chemokines and CCR1 in peripheral immune cells. The peripheral upregulation of these chemokines; may reduce the chemoattraction of immune cells to the central nervous system and thus add to the therapeutic effects of interferon beta.