白细胞介素 32γ（IL-32γ）在美洲皮肤利什曼病患者的皮肤和黏膜病变中高度表达：与肿瘤坏死因子（TNF）和白细胞介素 10 相关。

BACKGROUND: The interleukin 32 (IL-32) is a proinflammatory cytokine produced by immune and non-immune cells. It can be induced during bacterial and viral infections, but its production was never investigated in protozoan infections. American Tegumentary Leishmaniasis (ATL) is caused by Leishmania protozoan leading to cutaneous, nasal or oral lesions. The aim of this study was to evaluate the expression of IL-32 in cutaneous and mucosal lesions as well as in peripheral blood mononuclear cells (PBMC) exposed to Leishmania (Viannia) braziliensis. METHODS: IL-32, tumour necrosis factor (TNF) and IL-10 protein expression was evaluated by immunohistochemistry in cutaneous, mucosal lesions and compared to healthy specimens. The isoforms of IL-32α, β, δ, γ mRNA, TNF mRNA and IL-10 mRNA were assessed by qPCR in tissue biopsies of lesions and healthy skin and mucosa. In addition, PBMC from healthy donors were cultured with amastigotes of L. (V.) braziliensis. In lesions, the parasite subgenus was identified by PCR-RFLP. RESULTS: We showed that the mRNA expression of IL-32, in particular IL-32γ was similarly up-regulated in lesions of cutaneous (CL) or mucosal (ML) leishmaniasis patients. IL-32 protein was produced by epithelial, endothelial, mononuclear cells and giant cells. The IL-32 protein expression was associated with TNF in ML but not in CL. IL-32 was not associated with IL-10 in both CL and ML. Expression of TNF mRNA was higher in ML than in CL lesions, however levels of IL-10 mRNA were similar in both clinical forms. In all lesions in which the parasite was detected, L. (Viannia) subgenus was identified. Interestingly, L. (V.) braziliensis induced only IL-32γ mRNA expression in PBMC from healthy individuals. CONCLUSIONS: These data suggest that IL-32 plays a major role in the inflammatory process caused by L. (Viannia) sp or that IL-32 is crucial for controlling the L. (Viannia) sp infection.

背景：白细胞介素 32（IL-32）是一种由免疫和非免疫细胞产生的促炎细胞因子。它可以在细菌和病毒感染期间被诱导，但从未在原生动物感染中研究过其产生。美洲皮肤利什曼病（ATL）是由原生动物利什曼引起的，导致皮肤、鼻腔或口腔病变。本研究旨在评估白细胞介素 32（IL-32）在皮肤和粘膜病变以及暴露于 Leishmania（Viannia）braziliensis 的外周血单个核细胞（PBMC）中的表达。

方法：通过免疫组织化学评估皮肤、粘膜病变以及与健康标本相比的白细胞介素 32（IL-32）、肿瘤坏死因子（TNF）和白细胞介素 10（IL-10）蛋白表达。通过 qPCR 评估组织活检中病变和健康皮肤和粘膜的 IL-32α、β、δ、γ mRNA、TNF mRNA 和 IL-10 mRNA 同工型。此外，从健康供体的 PBMC 中培养 L.（V.）braziliensis 无鞭毛体。在病变中，通过 PCR-RFLP 鉴定寄生虫亚属。

结果：我们表明，皮肤（CL）或粘膜（ML）利什曼病患者的病变中 IL-32，特别是 IL-32γ 的 mRNA 表达相似地上调。IL-32 蛋白由上皮细胞、内皮细胞、单核细胞和巨细胞产生。在 ML 中，IL-32 蛋白表达与 TNF 相关，但在 CL 中则不然。CL 和 ML 中 IL-32 与 IL-10 均无关。ML 病变中 TNF mRNA 的表达高于 CL 病变，但两种临床形式的 IL-10 mRNA 水平相似。在检测到寄生虫的所有病变中，均鉴定出 L.（Viannia）亚属。有趣的是，L.（V.）braziliensis 仅诱导来自健康个体的 PBMC 中 IL-32γ mRNA 的表达。

结论：这些数据表明，IL-32 在 L.（Viannia）sp 引起的炎症过程中起主要作用，或者 IL-32 对控制 L.（Viannia）sp 感染至关重要。