Interferon (IFN)-gamma , tumor necrosis factor-alpha , interleukin-6, and IFN-gamma receptor 1 are the major immunological determinants associated with post-kala azar dermal leishmaniasis.
Interferon (IFN)-gamma , tumor necrosis factor-alpha , interleukin-6, and IFN-gamma receptor 1 are the major immunological determinants associated with post-kala azar dermal leishmaniasis.
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干扰素 (IFN)-γ、肿瘤坏死因子-α、白介素-6 和 IFN-γ 受体 1 是与黑热病后皮肤利什曼病相关的主要免疫决定因素。
DOI：
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发表时间：
2006
影响因子：
6.4
通讯作者：
P. Salotra
中科院分区：
文献类型：
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作者：
N. Ansari;V. Ramesh;P. Salotra
应用半定量逆转录聚合酶链反应（RT-PCR）技术检测了28例黑热病后皮肤利什曼病（PKDL）和14例黑热病（KA）患者皮损内细胞因子基因的表达。数据显示混合的T辅助细胞1型（Th 1）和T辅助细胞2型（Th 2）应答，如干扰素（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表达升高所反映的，而IFN-γ受体1的表达最小（IFN-γ R1）mRNA在PKDL病变中的表达与正常皮肤组织相比。与KA病变相比，PKDL病变中IFN-γ、TNF-α和IL-6的mRNA水平显著升高，这意味着这些细胞因子在PKDL发病机制中起重要作用。在IFN-γ和TNF-α水平升高的情况下，对PKDL中1型效应子活性的干扰可能是由于IFN-γ R1基因的最小表达或同时存在具有抵消作用的IL-10、IL-6和TGF-β水平升高。治疗后，IFN-γ R1在mRNA和蛋白质水平的恢复，加上抵消细胞因子的下调，可能有助于与IFN-γ相关的信号的作用，产生寄生虫清除。因此，PKDL中不利的临床演变可能不是由于病灶内Th 1应答的缺乏，而是可能是由于伴随沿着IFN-γ R1下调的抵消性细胞因子的存在。
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-beta , 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-gamma R1.