Laboratory of Immunology, Universidade Federal do Triângulo Mineiro, Uberaba, Minas Gerais, Brazil.
PLoS Negl Trop Dis. 2011 Mar 8;5(3):e976. doi: 10.1371/journal.pntd.0000976.
TNF-alpha plays an important role in trypanocidal mechanisms and is related to tissue injury. This cytokine has been detected in the heart of human chagasic patients where it is associated with tissue damage. This study investigated whether TNF-alpha levels and the presence of genetic polymorphisms are associated with the presence of T. cruzi infection and/or with the development of the cardiac form in chronic chagasic patients. Genomic DNA of 300 subjects from an endemic area was extracted and analyzed by PCR using specific primers. TNF-alpha was assayed in culture supernatants by ELISA. An association was observed between the absence of the TNF-238A allele and negative serology. Furthermore, seropositive individuals carrying the TNF-238A allele produced significantly higher TNF-alpha levels without stimulation (p=0.04) and after stimulation with LPS (p=0.007) and T. cruzi antigens (p=0.004). The present results suggest that the polymorphism at position -238 influences susceptibility to infection and that this allele is associated with higher TNF-alpha production in seropositive individuals.
TNF-α 在杀锥虫机制中发挥重要作用，与组织损伤有关。该细胞因子已在人类恰加斯病患者的心脏中被检测到，与组织损伤有关。本研究旨在探讨 TNF-α 水平和遗传多态性的存在是否与 T. cruzi 感染的存在以及慢性恰加斯病患者心脏形式的发展有关。从流行地区提取 300 名受试者的基因组 DNA，并用特异性引物进行 PCR 分析。通过 ELISA 测定培养上清液中的 TNF-α。TNF-238A 等位基因缺失与血清学阴性呈显著相关。此外，携带 TNF-238A 等位基因的血清阳性个体在未经刺激（p=0.04）和 LPS 刺激（p=0.007）以及 T. cruzi 抗原刺激（p=0.004）后产生显著更高水平的 TNF-α。本研究结果表明，-238 位的多态性影响感染易感性，该等位基因与血清阳性个体中 TNF-α 的产生增加有关。
