Etretinate augments interferon beta-1b effects on suppressor cells in multiple sclerosis
Etretinate augments interferon beta-1b effects on suppressor cells in multiple sclerosis
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DOI：
10.1001/archneur.58.1.87
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发表时间：
2001-01-01
影响因子：
--
通讯作者：
Arnason, BGW
中科院分区：
文献类型：
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作者：
Qu, ZX;Pliskin, N;Arnason, BGW
背景：β干扰素治疗多发性硬化症（MS）仅部分有效，提示其在后续治疗中的潜在作用。类维生素A可增强1型干扰素在癌症患者中的临床疗效。我们推断，在MS中也可能存在同样的情况。在体外将干扰素β-1b加入外周血单个核细胞中可部分逆转MS患者的CD 8抑制细胞缺陷。将全反式视黄酸加入未经治疗的MS患者或对照组的外周血单个核细胞中可增强干扰素β-1b在体外增强CD 8抑制细胞功能的能力。确定正在接受干扰素β-lb治疗的MS患者给予类维生素A是否能增强其CD 8抑制细胞功能。参与者：正在接受干扰素β-1b治疗的MS患者，14例继发性进展型MS患者和3例复发缓解型MS患者。结果：17例MS患者接受了长达6个月的etretinate治疗。计划给药为第一口10 mg，每日3次，第二和第三个月25 ms，每日2次，此后10 mg，每日2次。25 mg每日一次的剂量耐受性不佳，在1期临床试验中直至第3个月的14例患者中，1例患者需要将剂量降至10 mg每日三次，4例患者需要将剂量降至10 mg每日两次。11名患者完成了试验。在1、3和6个月时，与基线值相比，依维甲酸治疗显著增强抑制功能。在1期临床试验过程中，未观察到残疾或生活质量发生有意义的变化。计算机的神经心理学测试表明，在6个月的言语记忆的选定方面相比，基线values.Conclusions：Etretinate治疗剂量为10毫克两次或三次，每天增强抑制细胞功能的MS患者接受干扰素β-lb。MS患者对更高剂量的依维A酯治疗（25 mg，每日两次）耐受性较差。即使在10 mg，每日两次时，涉及粘膜和皮肤的不良反应对某些患者（但不是所有患者）也会造成麻烦。是否脉冲治疗或维甲酸的管理限制到一天的干扰素β给药也将增加抑制功能，同时更好地耐受，仍有待确定。
Background: Interferon beta treatment is only partially effective in multiple sclerosis (MS) suggesting a potential role for adjunctive therapies. Retinoids can augment the clinical efficacy of type 1 inteferons in patients with cancer. We reasoned that the same might hold in MS. Interferon beta-1b added to peripheral blood mononuclear cells in vitro partially reverses the CD8 suppressor cell defect of patients with MS. All-trans retinoic acid added to peripheral blood mononuclear cells from untreated patients with MS or from controls potentiates this ability of interferon beta-1b to augment CD8 suppressor cell function in vitro.Objective: To determine whether retinoid administration to patients with MS who are being treated with interferon beta-lb augments their CD8 suppressor cell function.Setting: A university hospital MS clinic. Particpants Patients with MS who were being treated with interferon beta-1b, 14 patients with secondary progressive MS and 3 patients with relapsing remitting MS.Results: Seventeen patients with MS received etretinate treatment For up to 6 months. Planned dosing was 10 mg 3 times daily for the first mouth, 25 ms twice daily for the second and third months, and 10 mg twice daily thereafter. The 25-mg tu ice daily dose was not well tolerated and of the 14 patients who remained in the phase 1 clinical trial through month 3 dose reduction to 10 mg thrice daily was required in 1 patient and to 10 mg twice daily in 4 patients. Eleven patients completed the trial. Etretinate treatment significantly augmented suppressor function over baseline values at 1, 3, and 6 months. No meaningful change was noted in disability or quality of life over the course of the phase 1 clinical trial. Neuropsychological testing of computers suggested improvement on selected aspects of verbal memory at 6 months compared with baseline values.Conclusions: Etretinate treatment at a dose of 10 mg twice or three times daily augments suppressor cell function in patients with MS receiving interferon beta-lb. Higher dose etretinate treatment (25 mg twice daily) is poorly tolerated by patients with MS. Even at 10 mg twice daily adverse experiences involving the mucous membranes and the skin become troublesome for some, but not all, patients. Whether pulse therapy or administration of retinoid restricted to the day of interferon beta dosing will also augment suppressor function, while being better tolerated, remains to be determined.