Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia - Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Cytokine. 2013 May;62(2):302-9. doi: 10.1016/j.cyto.2013.03.001. Epub 2013 Apr 2.
Despite the evidences showing the relevance of regulatory immune-mediated mechanisms to guarantee the stable graft function in renal transplanted patients, studies focusing on the immune response observed over a long-term period after renal transplantation are still limited. Several efforts have been done to establish novel biomarkers with relevant predictive values that could be used as prognostic laboratorial tools to monitor the complex network triggered through time after kidney transplantation. In this study, we have evaluated the pro-inflammatory and regulatory patterns of plasma cytokines in a group of 120 renal transplanted patients with stable graft function ranging from 1 to 160 months. Our data demonstrated an overall predominance of regulatory cytokines short-term after renal transplantation (1-24 months) with peaks of IL-4, IL-5 and IL-10. Moreover, a slight peak of TNF-α was observed 25-60 months after renal transplantation. Following a gap of stable cytokine profile (61-120 months), peaks of pro-inflammatory cytokines IL-8, IL-6, IL1β, TNF-α and IL-12 were observed later on (>120 months) after renal transplantation. Additionally, the categorical analysis of "low" or "high" cytokine producers re-enforce the occurrence of an overall regulatory status early-after stable renal graft function with a predominant pro-inflammatory pattern later on long-term renal transplantation. Taken together, our data suggest that IL-5 is a good biomarker associated with short-term stable renal function, whereas IL-12 seems to be a relevant pro-inflammatory element in long-term renal transplanted patients.
尽管有证据表明调节性免疫介导机制对于保证肾移植患者稳定的移植物功能至关重要,但对于肾移植后长期观察到的免疫反应的研究仍然有限。已经做了一些努力来建立具有相关预测价值的新型生物标志物,这些标志物可以作为预后的实验室工具,以监测肾移植后随时间推移而触发的复杂网络。在这项研究中,我们评估了 120 例稳定肾功能(1 至 160 个月)的肾移植患者血浆细胞因子的促炎和调节模式。我们的数据显示,肾移植后短期(1-24 个月)总体上以调节性细胞因子占优势,IL-4、IL-5 和 IL-10 达到峰值。此外,在肾移植后 25-60 个月观察到 TNF-α 的轻微峰值。在稳定的细胞因子谱(61-120 个月)之后,随后观察到促炎细胞因子 IL-8、IL-6、IL1β、TNF-α 和 IL-12 的峰值(>120 个月)。此外,对“低”或“高”细胞因子产生者的分类分析,在稳定的肾移植功能后早期再次证实了总体调节状态的发生,随后在长期肾移植中出现了促炎模式。总之,我们的数据表明,IL-5 是与短期稳定肾功能相关的良好生物标志物,而 IL-12 似乎是长期肾移植患者中相关的促炎因素。