Panagio Luciano A, Tristao Fabrine S M, Moreira Ana P, Pereira Marcelo S F, Cavassani Karen A, Milanezi Cristiane M, Rossi Marcos A, Silva João S
Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
Med Mycol. 2008 Aug;46(5):435-42. doi: 10.1080/13693780801895444. Epub 2008 Mar 5.
Interleukin (IL)-18 has been regarded as a Th1 type cytokine involved in many fungal and parasitic infections. Since there have been no studies, as of yet, evaluating the role of this cytokine in paracoccidioidomycosis (PCM), we assessed the function of IL-18 by using an experimental PCM model. Our results showed that IL-18 knockout (IL-18 -/-) BALB/c were more resistant to Paracoccidioides brasiliensis than their littermate controls (WT). In fact, mortality rate was higher in WT mice and in the first month of infection, the number of colony forming units of the etiologic agent recovered from the lungs was greater in WT mice. In histopathological analyses, well-formed granulomas were seen in both WT and IL-18(-/-) mice. However, substantial differences were observed at the second month of infection when epithelioid cells predominated in the lesions of IL-18(-/-) mice, which could infer that IL-18 postpones pulmonary healing. The levels of IL-10 were significantly higher in IL-18 sufficient mice at early stages of infection and therefore account for the delayed fungal clearance observed in WT mice. TNF-alpha augmented later in the infection of WT mice, seemingly to compensate high levels of IL-10. Our results demonstrated that IL-18 has a critical role in protecting BALB/c mice against disseminated PCM.
白细胞介素（IL）-18被认为是一种参与多种真菌和寄生虫感染的Th1型细胞因子。由于截至目前尚无研究评估这种细胞因子在副球孢子菌病（PCM）中的作用，我们通过使用实验性PCM模型评估了IL-18的功能。我们的结果表明，IL-18基因敲除（IL-18 -/-）的BALB/c小鼠比其同窝对照（WT）对巴西副球孢子菌更具抵抗力。事实上，WT小鼠的死亡率更高，并且在感染的第一个月，从WT小鼠肺部回收的病原体的集落形成单位数量更多。在组织病理学分析中，WT和IL-18（-/-）小鼠均可见形成良好的肉芽肿。然而，在感染的第二个月观察到了显著差异，此时IL-18（-/-）小鼠病变中上皮样细胞占主导，这可能意味着IL-18会延迟肺部愈合。在感染早期，IL-18充足的小鼠中IL-10水平显著更高，因此这可以解释在WT小鼠中观察到的真菌清除延迟现象。在WT小鼠感染后期，TNF-α水平升高，似乎是为了补偿高水平的IL-10。我们的结果表明，IL-18在保护BALB/c小鼠免受播散性PCM感染方面具有关键作用。
