Yang C W, Wu M S, Pan M J
Department of Nephrology, Chang Gung Memorial Hospital and Graduate Institute of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
Nephrol Dial Transplant. 2001;16 Suppl 5:73-7. doi: 10.1093/ndt/16.suppl_5.73.
Leptospirosis is a re-emerging infectious disease, affecting both animals and humans worldwide. Multiple organ involvement may be encountered in leptospirosis, and early renal involvement is very common, characterized by tubulo-interstitial nephritis and tubular dysfunction. All 12 patients diagnosed in Chang Gung Memorial Hospital (Taiwan) between 1997 and 1999 had acute renal failure, with five patients requiring dialysis. Leptospira shermani is the main serovar encountered in Taiwan, and penicillin may dramatically rescue patients from multiple organ failure provided it is given early. To understand the mechanism behind tubular injuries by leptospira infection, outer membrane proteins (OMPs) extracted from pathogenic leptospira were given to tubular cells in culture. Our in vitro experiment showed that OMPs of pathogenic leptospira activate nuclear NFkappaB binding and stimulate downstream inducible nitric oxide (iNOS), monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) expression. These results indicate that leptospiral infection may induce tubulo-interstitial nephritis through a toxic component in the outer membrane followed by expression of inflammatory genes.
钩端螺旋体病是一种再度出现的传染病,在全球范围内影响动物和人类。钩端螺旋体病可能会出现多器官受累,早期肾脏受累非常常见,其特征为肾小管间质性肾炎和肾小管功能障碍。1997年至1999年期间在台湾长庚纪念医院确诊的所有12例患者均患有急性肾衰竭,其中5例患者需要透析。谢氏钩端螺旋体是台湾地区主要的血清型,若早期给予青霉素,可显著使患者从多器官衰竭中获救。为了解钩端螺旋体感染导致肾小管损伤的机制,将从致病性钩端螺旋体中提取的外膜蛋白(OMPs)加入培养的肾小管细胞中。我们的体外实验表明,致病性钩端螺旋体的OMPs可激活核NFκB结合并刺激下游诱导型一氧化氮(iNOS)、单核细胞趋化蛋白-1(MCP-1)和肿瘤坏死因子-α(TNF-α)的表达。这些结果表明,钩端螺旋体感染可能通过外膜中的一种毒性成分诱导肾小管间质性肾炎,随后引发炎症基因的表达。