Gomes-Silva A, de Cássia Bittar R, Dos Santos Nogueira R, Amato V S, da Silva Mattos M, Oliveira-Neto M P, Coutinho S G, Da-Cruz A M
Laboratório de Imunoparasitologia, Departamento de Imunologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
Clin Exp Immunol. 2007 Sep;149(3):440-4. doi: 10.1111/j.1365-2249.2007.03436.x. Epub 2007 Jul 5.
Suitable levels of interferon (IFN)-gamma and interleukin (IL)-10 seem to favour the outcome of cutaneous leishmaniasis (CL), while high IFN-gamma and low IL-10 production are associated with severity of mucosal leishmaniasis (ML). Considering that cytokine balance is important for the maintenance of protective responses in leishmaniasis, our aim was to investigate leishmanial antigens-induced IFN-gamma and IL-10 levels maintained in healed individuals who had different clinical outcomes of Leishmania infection. Thirty-three individuals who recovered from L. braziliensis infection were studied: cured CL (CCL), cured ML (CML), spontaneous healing of CL (SH) or asymptomatic individuals (ASY). Cytokines were quantified by enzyme-linked immunosorbent assay (ELISA) in culture supernatants of L. braziliensis-stimulated peripheral blood mononuclear cells (PBMC). IFN-gamma levels were higher in CML (7593 +/- 5994 pg/ml) in comparison to SH (3163 +/- 1526 pg/ml), ASY (1313 +/- 1048 pg/ml) or CCL (1897 +/- 2087 pg/ml). Moreover, cured ML cases maintained significantly lower production of IL-10 (127 +/- 57.8 pg/ml) in comparison to SH (1373 +/- 244 pg/ml), ASY (734 +/- 233 pg/ml) or CCL (542 +/- 375 pg/ml). Thus, a high IFN-gamma/IL-10 ratio observed in CML can indicate unfavourable cytokine balance. On the other hand, no significant difference in the IFN-gamma/IL-10 ratio was observed when CCL individuals were compared to SH or ASY subjects. In conclusion, even after clinical healing, ML patients maintained a high IFN-gamma/IL-10 secretion profile in response to leishmanial antigens. This finding can explain a delayed down-modulation of exacerbated inflammatory responses, which can be related in turn to the necessity of prolonged therapy in ML management. Conversely, lower IFN-gamma/IL-10 balance observed in CCL, SH and ASY individuals can represent a better-modulated immune response associated with a favourable prognosis.
合适水平的干扰素(IFN)-γ和白细胞介素(IL)-10似乎有利于皮肤利什曼病(CL)的转归,而高IFN-γ产生和低IL-10产生与黏膜利什曼病(ML)的严重程度相关。鉴于细胞因子平衡对于利什曼病中保护性反应的维持很重要,我们的目的是研究利什曼原虫抗原诱导的IFN-γ和IL-10水平,这些水平在利什曼原虫感染有不同临床转归的痊愈个体中得以维持。对33名从巴西利什曼原虫感染中康复的个体进行了研究:治愈的CL(CCL)、治愈的ML(CML)、CL自发愈合(SH)或无症状个体(ASY)。通过酶联免疫吸附测定(ELISA)对巴西利什曼原虫刺激的外周血单个核细胞(PBMC)培养上清液中的细胞因子进行定量。与SH(3163±1526 pg/ml)、ASY(1313±1048 pg/ml)或CCL(1897±2087 pg/ml)相比,CML中的IFN-γ水平更高(7593±5994 pg/ml)。此外,与SH(1373±244 pg/ml)、ASY(734±233 pg/ml)或CCL(542±375 pg/ml)相比,治愈的ML病例中IL-10的产生显著更低((127±57.8 pg/ml)。因此,在CML中观察到的高IFN-γ/IL-10比值可能表明细胞因子平衡不利。另一方面,将CCL个体与SH或ASY个体进行比较时,未观察到IFN-γ/IL-10比值有显著差异。总之,即使在临床治愈后,ML患者对利什曼原虫抗原仍保持高IFN-γ/IL-10分泌谱。这一发现可以解释加剧的炎症反应的延迟下调,这反过来可能与ML治疗中延长治疗的必要性有关。相反,在CCL、SH和ASY个体中观察到的较低IFN-γ/IL-10平衡可能代表与良好预后相关的更好调节的免疫反应。
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