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。
