目的：观察干扰素-α（interferon-α，IFN-α）在羟基脲（hydroxycarbmide，OHU）治疗慢性粒细胞白血病（chronic myelocytic leukemia，CML）中对嗜酸性粒细胞（eosinophile granulocyte，EOS）抗白血病免疫效应的增强作用，并探讨其相关的免疫机制。 方法： 收集 2010年1月至2012年2月间解放军第148中心医院诊治的46例BCR-ABL阳性的CML初治患者，分为OHU单独治疗组（20例）和OHU联合IFN-α治疗组（26例），两组患者的性别比例、年龄范围和疾病分期等基本均衡；同时采集本院查体中心30名健康志愿者的标本作为对照。ELISA法检测患者治疗前后血清中IL-6、IL-12、IL-17和IFN-γ的水平；细胞化学染色法检测患者骨髓细胞中过氧化物酶（peroxydase，POX）的活性，免疫荧光（immunofluorescence，IF）染色检测CML患者骨髓中IL-12、IL-17A和甘露糖受体（mannose receper，MR）的表达情况。 结果： CML患者血清IL-6、IL-12和IL-17含量较健康志愿者显著升高\[（116.13?15.16） vs （90.98?12.32）pg/ml，（189.26?22.14）vs （96.60?4.92）pg/ml，（34.42?2.16） vs（2374?1.36）pg/ml；均P<0.05\]。单纯OHU治疗后，CML患者血清中IL-6、IL-12和IL-17的水平显著下降\[分别为（87.14?1337）、（60.22?20.16）、（17.03?2.16）pg/ml，均P<0.05\]；与单纯OHU治疗组相比，OHU 联合IFN-α组患者血清中IL-6、IL-12和IL-17的水平显著上调\[（122.04?10.25）、（101.12?27.16）和（40.16?4.11）pg/ml，P<0.05或P<001\]。CML患者骨髓中EOS阳性表达IL-12、IL-17A和MR。IFN-α联合OHU治疗能减轻OHU对EOS的免疫抑制效应，患者骨髓中IL-12、IL-17A水平和MR阳性EOS数量较单纯OHU治疗组显著增加，且POX活性增强。 结论： CML患者的EOS能分泌IL-12和IL-17，并表达MR。IFN-α联合OHU治疗能增强EOS的抗白血病效应，减轻OHU对EOS的免疫抑制作用。

Objective： To observe the immunological enhancement effect of interferon-α (IFN-α) on anti-leukemia activity of eosinophils granulocytes (EOSs) in patients with chronic myelogenous leukemia (CML) after hydroxycarbmide (OHU) therapy, and to investigate the related immunologic mechanism. Methods: Forty-six BCR-ABL positive CML patients (from Jan. 2010 to Feb. 2012) admitted in the 148th Hospital of PLA were included in this study, and were divided into OHU group (20 cases) and OHC combined IFN-α group (26 cases) with a balance in sex ratio and age range. Meanwhile, specimens of 30 healthy volunteers from the Regular Physical Examination Center of the hospital were collected as control. ELISA was used to determine the concentrations of cytokines IL-6, IL-12, IL-17 and IFN-γ in serum of the CML patients. Cytochemistry staining was used to observe the peroxydase (POX) expression of immunocyte in bone marrow. Immunofluorescence (IF) staining was used to observe cytokines IL-12 and IL-17A expression levels as well as the expression of mannose receptor (MR). Results: The serum concentrations of IL-6, IL-12 and IL-17 were increased significantly in CML patients compared with the healthy control group \[(116.13?15.16) vs (90.98?12.32) pg/ml; (189.26?22.14) vs (96.60?4.92) pg/ml; (34.42?2.16) vs (23.74?1.36) pg/ml, P<0.05\]. After OHU treatment, the serum concentrations of IL-6, IL-12 and IL-17 in the CML patients decreased to (87.14?13.37) , (60.22?20.16) and (17.03?2.16) pg/ml, respectively (P<0.05). Compared with the OHU treatment group, the serum IL-6, IL-12 and IL-17 concentrations in the OHU combined IFN-α treatment group were significantly up-regulated \[(122.04?1025), (101.12?27.16) and (40.16?4.11) pg/ml, P<0.05 or P<0.01\]. EOS in bone marrow of CML patients expressed IL-12, IL-17A and MR. OHU treatment combined with IFN-α could decrease immunosuppressive effect of OHU therapy, the quantity of EOS with positive IL-12, IL-17A and MR expressions was increased obviously, and the POX activity of EOS was also increased. Conclusion: EOS can secrete cytokines IL-12 and IL-17 and express MR. OHU treatment combined with IFN-α can enhance the anti-leukemia immunological effect of EOS and decrease the immunosuppressive effect of OHU therapy on EOS.

济南军区“十二五”科技发展计划重点支持项目（No. JN11LO17）