沙利度胺对骨髓瘤患者免疫学的影响

Immunoreactivity of thalidomide in patients with multiple myeloma

目的 :从免疫学角度了解沙利度胺治疗难治性复发性多发性骨髓瘤的机制。方法 :用双抗夹心法ELISA动态检测经沙利度胺治疗后多发性骨髓瘤 (MM )患者的IL 6 ,IL 10 ,IL 4,TNF α水平 ,用RT PCR半定量法检测瘤细胞以上 4种细胞因子mRNA的表达。结果 :口服沙利度胺 2 0 0mg·d-114d时 ,IL 6 ,IL 10和TNF α水平无明显变化 ,而IL 4水平开始升高 ,并随时间和沙利度胺剂量增加而增加 ,口服沙利度胺 40 0mg·d-114d ,2 8d ,5 6d ,84d时 ,IL 6 ,IL 10和TNF α水平均下降 ,随时间延长 ,下降越明显。瘤细胞内IL 6 ,IL 10的mRNA表达无明显变化 ,IL 4的mRNA表达增加发生在口服 40 0mg·d-1沙利度胺 2 8d时 ,TNF α的mRNA表达减少与血清TNF α水平下降时间一致。结论 :沙利度胺可通过降低MM患者的IL 6 ,IL 10 ,TNF α和增加IL 4的水平而发挥抗骨髓瘤的作用 ,对以上 4种因子水平的影响 ,有些单独与直接减少瘤细胞mRNA的表达有关 (TNF α) ;有些是通过增加瘤细胞mRNA表达和瘤细胞外的共同作用 (IL 4) ;而IL 6和IL

Objective:To study immunologically the therapeutic mechanism of thalidomide in treatment of refractory,replapsed,multiple myeloma.Methods:The serum level of IL 6,IL 10,IL 4,and TNF α and their mRNA express in patients who have been treated with thalidomide were measured by ELISA and RT PCR method respectively.Results:At the 14th day of oral 200 mg thalidomide,the IL 4 level was elevated with the increase of dosage and the elapse of time and no changes occurred to IL 6,IL 10 and TNF α.At the 14th,28th,56th,84th day after dosing 400 mg thalidomide,the IL 6,IL 10 and TNF α were commencing to decrease and significantly decreased with the increase of dose and the passage of time.The mRNA express of IL 4 was increased at the 28th day of dosing and the decrease in mRNA express of TNF α was in line with the decrease of serum TNF α level.Conclusion:The anti myeloma effect of thalidomide is achieved by decreasing IL 6,IL 10 or TNF α level and increasing IL 4 level.The serum level of these 4 factors may be directly related to decrease of mRNA expression (TNF α) or related to increase of mRNA expression and cells other than myeloma cells.