Interferon (IFN)-γ tumor necrosis factor-α, interleukin-6, and IFN-γ receptor 1 are the major immunological determinants associated with post-kala azar dermal leishmaniasis
Interferon (IFN)-γ tumor necrosis factor-α, interleukin-6, and IFN-γ receptor 1 are the major immunological determinants associated with post-kala azar dermal leishmaniasis
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DOI：
10.1086/506624
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发表时间：
2006-10-01
影响因子：
6.4
通讯作者：
Salotra, Poonam
中科院分区：
文献类型：
--
作者：
Ansari, Nasim A.;Ramesh, Venkatesh;Salotra, Poonam
采用半定量逆转录聚合酶链反应对28例黑热病后皮肤利什曼病（PKDL）和14例黑热病（KA）患者的病灶内细胞因子基因表达进行了分析。数据显示，与正常皮肤组织相比，PKDL病变中干扰素(IFN)- γ、肿瘤坏死因子(TNF)- α、转化生长因子(TGF)- β、白细胞介素(IL)-10、IL-6和IL-4 mRNA的表达升高，IFN- γ受体1 (IFN- γ R1) mRNA的表达极少，这反映了1型辅助T细胞（Th1）和2型辅助T细胞（Th2）的混合反应。与KA病变相比，PKDL病变中ifn - γ、tnf - α和IL-6 mRNA水平显著升高，提示这些细胞因子在PKDL发病中起重要作用。在ifn - γ和tnf - α水平升高的情况下，对PKDL中1型效应物活性的干扰可能是由于ifn - γ R1基因的最低表达或同时存在IL-10、IL-6和TGF-b水平升高，它们具有抵消作用。治疗后，ifn - γ R1 mRNA和蛋白水平的恢复，加上拮抗细胞因子的下调，可能促进ifn - γ相关信号的作用，产生寄生虫清除。因此，PKDL的不利临床进展可能不是由于没有病灶内Th1反应，而是由于抵抗细胞因子的存在以及IFN-gR1的下调。
Semiquantitative reverse-transcription polymerase chain reaction was used to analyze intralesional cytokine gene expression in 28 patients with post-kala azar dermal leishmaniasis (PKDL) and 14 patients with kala azar (KA). The data revealed mixed T helper cell type 1 (Th1) and T helper cell type 2 (Th2) responses, as reflected by elevated expression of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, interleukin (IL)-10, IL-6, and IL-4 mRNA, with minimal expression of IFN-gamma receptor 1 (IFN-gamma R1) mRNA in PKDL lesions, compared with that in normal skin tissue. In comparison with those in KA lesions, mRNA levels for IFN-gamma, TNF-alpha, and IL-6 were found to be significantly elevated in PKDL lesions, implying that these cytokines play an important role in PKDL pathogenesis. In the presence of elevated levels of IFN-gamma and TNF-alpha, interference with type 1 effector activity in PKDL may be due to minimal expression of the IFN-gamma R1 gene or the simultaneous presence of elevated levels of IL-10, IL-6, and TGF-b, which have counteracting effects. After treatment, the restoration of IFN-gamma R1 at both mRNA and protein levels, coupled with down-regulation of counteracting cytokines, may facilitate the action of signals associated with IFN-gamma, yielding parasite clearance. Therefore, unfavorable clinical evolution in PKDL may not be due to the absence of an intralesional Th1 response but rather may be due to the presence of counteracting cytokines along with the down-modulation of IFN-gR1.