U. S. Department of Health and Human Services, Health Resources and Services Administration, National Hansen's Disease Programs, Lab Research Branch at Louisiana State University, Baton Rouge, LA 70803, United States.
Int Immunopharmacol. 2010 Apr;10(4):487-92. doi: 10.1016/j.intimp.2010.01.010. Epub 2010 Feb 1.
Thalidomide (Thal) provides effective treatment for erythema nodosum leprosum (ENL). In combination with Dexamethasome (Dex) it is an effective treatment for multiple myeloma (MM) and Waldenström's macroglobulinemia (WM). Thal's mechanism(s) of action in the treatment of these diverse medical conditions is not known, but it could be suppression of immunoglobulin (Ig) synthesis. Mononuclear cells were stimulated with pokeweed (PWM), and treated with Thal, Thal+Dex or Dex. The cultures were assayed for IgM and IgG. The maximum synthesis was expected to occur in cultures stimulated with PWM at 0.5, 5.0 or 10 microg/ml. The test agents at 15 microM each were expected to alter the response. Compared to cultures stimulated with PWM alone, there was significantly less Ig in the cultures containing Thal+PWM, and significantly more Ig in the cultures containing Thal+Dex+PWM or Dex+PWM (Wilcoxon). The median % of maximum was 57 for cultures treated with Thal+PWM; 184 for cultures treated with Thal+Dex+PWM, and 139 for cultures treated with Dex+PWM. Thal also acted as a co-stimulant with PWM and enhanced the synthesis of IL-2, IL-6 and DNA; whereas, Thal+Dex or Dex enhanced Ig synthesis, but suppressed IL-2, IL-6 and cell proliferation. Thal's ability to suppress Ig may explain its activity in ENL, MM and WM. The enhancement of Ig by Dex does not help to explain a role for Dex alone or in combination with Thal for the treatment of MM and WM.
沙利度胺(Thal)为红斑结节性麻风病(ENL)提供了有效的治疗方法。与地塞米松(Dex)联合使用时,它是多发性骨髓瘤(MM)和华氏巨球蛋白血症(WM)的有效治疗方法。Thal 在治疗这些不同医学病症中的作用机制尚不清楚,但可能是抑制免疫球蛋白(Ig)的合成。用美洲商陆(PWM)刺激单核细胞,并用 Thal、Thal+Dex 或 Dex 处理。培养物检测 IgM 和 IgG。预期在以 0.5、5.0 或 10μg/ml 刺激 PWM 的培养物中会发生最大合成。预计每个测试剂 15μM 会改变反应。与仅用 PWM 刺激的培养物相比,含 Thal+PWM 的培养物中的 Ig 明显减少,而含 Thal+Dex+PWM 或 Dex+PWM 的培养物中的 Ig 明显增加(Wilcoxon)。用 Thal+PWM 处理的培养物的中位数为 57%;用 Thal+Dex+PWM 处理的培养物的中位数为 184%;用 Dex+PWM 处理的培养物的中位数为 139%。Thal 还与 PWM 协同刺激,增强 IL-2、IL-6 和 DNA 的合成;而 Thal+Dex 或 Dex 增强 Ig 合成,但抑制 IL-2、IL-6 和细胞增殖。Thal 抑制 Ig 的能力可能解释其在 ENL、MM 和 WM 中的活性。Dex 增强 Ig 的作用并不能解释 Dex 单独或与 Thal 联合用于治疗 MM 和 WM 的作用。