环磷酰胺治疗尖锐湿疣最适剂量探讨

Optimal Dosage of Cyclophosphamide in Condyloma Acuminatum Treatment

目的探讨环磷酰胺(CTX)治疗尖锐湿疣(CA)的最适剂量,为临床治疗提供新思路。方法①初步确定最适剂量:66例先行CO2激光治疗的CA患者分为4组,其中3组分别口服CTX(25、50、75 mg/d),另一组激光治疗后未予药物处理,观察10 d、20 d、1月、2月、3月及6个月后皮损复发率;ELISA法检测CTX治疗前后患者外周血IL-2、IFN-γ、IL-4、IL-10水平,以10例健康志愿者作对照。②进一步验证:8例未行CO2激光治疗的患者直接口服CTX 50 mg/d,观察治疗后3月内皮损情况;RT-PCR检测CTX治疗前后皮损内IL-2、IFN-γ、IL-4、IL-10 mRNA水平,以6例健康人包皮组织作对照。结果①先行CO2激光治疗组复发情况:治疗第10天各组复发率差异无统计学意义;第20天以后,CTX 50 mg/d和75 mg/d治疗组的复发率较CTX 25 mg/d组和单纯激光组均明显下降(均P<0.05);服用CTX前,CA患者外周血IL-2、IFN-γ水平低于正常对照组(均P<0.05),IL-4、IL-10高于正常对照组(均P<0.05)。服用CTX后第10天,50 mg/d组和75 mg/d组的IL-2、IFN-γ水平显著提高,IL-4水平明显降低(均P<0.05)。②直接口服CTX 50 mg/d组皮损组织细胞因子表达情况:皮损处IL-2、IFN-γmRNA水平较治疗前升高,差异有统计学意义(均P<0.05),IL-4 mRNA表达较治疗前显著下降(P<0.01),IL-10 mRNA表达在治疗前后无明显差异。结论合适低剂量CTX能诱导CA患者Th1细胞因子IL-2、IFN-γ蛋白和mRNA的表达,抑制Th2细胞因子IL-4、IL-10蛋白和mRNA的表达;CTX 50~75 mg/d治疗CA能有效改善局部免疫功能,CTX 50 mg/d可能是CA治疗的最佳有效剂量。

Objective To explore the optimal dose of cyclophosphamide(CTX)in treatment of condyloma acuminatum(CA)and provide new ideas for clinic.Methods Sixty-six patients with CA after CO2 laser were divided into four groups,of which three groups were administered with cyclophosphamide(25,50,75 mg/day)and the other group served as laser control.The recurrence rate was observed after 10 days,20 days,1 month,2 months,3 months and 6 months.The levels of IL-2,IFN-γ,IL-4 and IL-10 in peripheral blood were measured by ELISA before and after the cyclophosphamide administration,ten healthy volunteers served as control.Eight patients without CO2 laser were directly administered with cyclophosphamide 50 mg/day and then their lesions were observed.The mRNA expression levels of IL-2,IFN-γ,IL-4 and IL-10 in the local lesions were measured by quantitative RT-PCR before and after the cyclophosphamide administration,the foreskine tissues of six healthy persons served as control.Results The recurrence rates in the patients after CO2 laser had no remarkable difference after 10 days of cyclophosphamide administration.However after 20 days,the recurrence rates decreased in 50 mg/day and 75 mg/day groups(5.56% and 6.67%,respectively,P<0.05),with remarkable differences as compared with the other groups.The serum levels of IL-2 and IFN-γ decreased remarkably while the levels of IL-4 and IL-10 increased remarkably(P<0.05)in CA patients compared with the healthy volunteers before the cyclophosphamide administration.The levels of IL-2,IFN-γ,IL-4,IL-10 in all the groups changed after treatment with cyclophosphamide for 10 days.The changes had the statistical significance(P<0.05)except the change in the group with a dose of 25 mg/day.The mRNA levels of IL-2 and IFN-γ in the local lesions of the patients without CO2 laser increased remarkably after the cyclophosphamide administration.While the mRNA level of IL-4 decreased very significantly after the treatment(P<0.01).However the mRNA level of IL-10 slightly decreased after the administration without a significant difference.Conclusion Suitable low-dose cyclophosphamide could induce the expression of Th1 cytokines such as IL-2 and IFN-γ in patients with CA and inhibit the expression of Th2 cytokines such as IL-4 and IL-10.The dose of cyclophosphamide 50-75 mg/day can effectively improve local immune function,50 mg/day may be the optimal effective dose for CA treatment.