Haslett Patrick A J, Roche Paul, Butlin C Ruth, Macdonald Murdo, Shrestha Niraj, Manandhar Rakesh, Lemaster Joe, Hawksworth Rachel, Shah Mahesh, Lubinsky A Steven, Albert Matthew, Worley Jason, Kaplan Gilla
Rockefeller University, New York, New York, USA.
J Infect Dis. 2005 Dec 15;192(12):2045-53. doi: 10.1086/498216. Epub 2005 Nov 10.
The immunomodulatory drug thalidomide is the treatment of choice for erythema nodosum leprosum (ENL), an inflammatory cutaneous and systemic complication of multibacillary leprosy. To elucidate the mechanism of action of thalidomide in this syndrome, we prospectively investigated 20 patients with ENL who were treated with thalidomide for 21 days. All patients responded to treatment, with the majority of them having complete resolution of cutaneous lesions within 7 days. This response was associated with a marked but transient increase in ex vivo mitogen-induced expression of interleukin (IL)-2 and interferon- gamma by CD4(+) and CD8(+) T cells that was observed on treatment day 7, but these returned to pretreatment levels by day 21. Plasma tumor necrosis factor- alpha levels were not high at baseline, and they increased modestly during treatment. Plasma levels of IL-12 increased steadily during thalidomide treatment. Hence, the therapeutic effect of thalidomide in ENL appears to be associated with transient immune stimulation, which suggests that the drug may promote an active immunoregulatory response.
免疫调节药物沙利度胺是结节性红斑麻风（ENL）的首选治疗药物，ENL是多菌型麻风的一种炎症性皮肤和全身性并发症。为了阐明沙利度胺在该综合征中的作用机制，我们前瞻性地研究了20例接受沙利度胺治疗21天的ENL患者。所有患者对治疗均有反应，大多数患者在7天内皮肤病变完全消退。这种反应与治疗第7天观察到的CD4(+)和CD8(+) T细胞体外丝裂原诱导的白细胞介素（IL）-2和干扰素-γ表达显著但短暂增加有关，但到第21天这些指标又恢复到治疗前水平。血浆肿瘤坏死因子-α水平在基线时不高，治疗期间略有升高。沙利度胺治疗期间血浆IL-12水平稳步升高。因此，沙利度胺对ENL的治疗作用似乎与短暂的免疫刺激有关，这表明该药物可能促进积极的免疫调节反应。
