FCR方案治疗的慢性淋巴细胞白血病患者血清IFN-γ、IL-4、IL-17及TGF-β水平变化

Alteration of IFN-γ,IL-4,IL-17 and TGF-β levels in Serum of Patients with Chronic Lymphocytic Leukemia Treated with FCR

目的:探讨FCR方案治疗前后慢性淋巴细胞白血病(CLL)患者血清中干扰素-γ(IFN-γ)、白介素-17(IL-17)、白介素-4(IL-4)和转化生长因子-β(TGF-β)水平变化及其临床意义。方法:选择接收过FCR方案治疗的CLL患者共计47例,30例健康体检者作为对照组,应用ELISA检测CLL患者治疗前后及对照组血清IFN-γ、IL-4、IL-17和TGF-β的水平。比较各组间IFN-γ、IL-4、IL-17和TGF-β水平、IFN-γ/IL-4比值及TGF-β/IL-17比值的差异。结果:CLL组患者治疗前IL-4、IL-17和TGF-β水平、TGF-β/IL-17比值均高于对照组,而IFN-γ水平及IFN-γ/IL-4比值均低于对照组(P<0.05);经过FCR方案治疗后,IL-4、IL-17和TGF-β水平、TGF-β/IL-17比值较治疗前明显下降(P<0.05),IFN-γ水平及IFN-γ/IL-4比值较治疗前明显上升(P<0.05)。治疗后的IL-4、IL-17水平、TGF-β/IL-17、IFN-γ/IL-4比值与对照组比较无明显差异(P>0.05),仅IFN-γ、TGF-β水平与对照组比较仍有统计学差异(P<0.05)。在Binet A期、B期和C期分期中,随着Binet分期进展,CLL患者血清IFN-γ、IL-17水平和IFN-γ/IL-4比值逐渐减低,血清IL-4水平、TGF-β/IL-17比值逐渐增高,治疗前CLL患者IFN-γ/IL-4比值与Binet分期均呈负相关(r=-0.53),TGF-β/IL-17比值与Binet分期均呈正相关(r=0.46)。根据治疗效果分组分析发现,治疗效果良好的CR组和PR组血清中IFN-γ、IL-4、IL-17、TGF-β水平、IFN-γ/IL-4、TGF-β/IL-17比值与治疗前比较,差异有统计学意义(P<0.05),而SD组和PD组与治疗前比较,差异无统计学意义(P>0.05)。结论:随着疾病进展,CLL患者IFN-γ/IL-4比值逐渐减低,TGF-β/IL-17比值逐渐增高,而FCR方案治疗可以克服这一趋势,动态监测IFN-γ/IL-4、TGF-β/IL-17比值的变化情况,因而可以指导临床治疗。

Objective： To investigate the alteration and clinical significance of IFN-γ,IL-4,IL-17 and TGF-β levels in serum of patients with chronic lymphocytic leukemia treated with FCR. Methods： Forty-seven CLL patients treated with FCR regimen were enrolled in CLL group,meanwhile 30 healthy persons were selected in control group. The serum levels of IFN-γ,IL-4,IL-17 and TGF-β were detected by ELISA in CLL group before and after treatment and in control group,then the differences of IFN-γ,IL-4,IL-17 and TGF-β levels as well as IFN-γ/IL-4 ratio and TGF-β/IL-17 ratio were compared between 2 groups. Results： Before treatment with PCR regimen,the IL-4,IL-17 and TGF-β levels as well as TGF-β/IL-17 in CLL group were higher than those in control group（ P〈0. 05）,while the IFN-γlevel and IFN-γ/IL-4 ratio in CLL group were lower than those in control group（ P〈0. 05）; after treatment with PCR regimen,the IL-4,IL-17 and TGF-β levels as well as TGF-β/IL-17 ratio all significantly decreased（ P〈0. 05）,while IFN-γ level and IFN-γ/IL-4 ratio significantly increased（ P〈0. 05） as compared with those before treatment,moreover,the IL-4 and IL-17 levels as well as TGF-β/IL-17 and IFN-γ/IL-4 ratio were no significantly different from those in control group（ P〉0. 05）,only the IFN-γ and TGF-β levels were significantly diffrent from control group（ P〈0. 05）. The analysis of Binet staging（ stage A,B,C） showed that along with pregression of Binet stages,the TGF-γ/IL-17 levels as well as the IFN-γ/IL-4 ratio in CLL group negatively correlated with Binet staging（ r =-0. 53）,while the TGF-β/IL-17 ratio positively correlated with Binet staging（ r = 0. 46）. The analysis of grouping accoraing to therapentic efficacy fonnd that the IL-4 and IL-17 levels and IFN-γ/IL-4 and TGF-β/IL-17 ratios in CR and PR groups were significantly different before and after treatment（ P〈0. 05）,while those in SD and PD groups did not showed statistical difference before and after treatment（ P〉0. 05） Conclusion： Along with the progression of disease,the IFN-γ/IL-4 ratio gradually decreases,and the TGF-β/L-17 ratio gradually increases. The treatment with FCR regimen can overcome this tread,therefore dynamically monitoring the chages of IFN-γ/IL-4 and TGF-β/L-17 ratios may contribute to guide the clinical treatment.