Department of Medicine B, University of Münster, Münster, Germany.
Mol Nutr Food Res. 2014 Jul;58(7):1474-90. doi: 10.1002/mnfr.201300818. Epub 2014 Apr 25.
In previous studies, we could show that the B vitamin nicotinamide (NAM) enhanced antimicrobial activity of neutrophils. Here, we assessed the effects of NAM in two models of experimental colitis.
Colitis was induced in C57BL/6 mice either by oral infection with Citrobacter rodentium or by DSS (dextran sodium sulphate) administration, and animals were systemically treated with NAM. Ex vivo bacterial clearance was assessed in murine and human whole blood, as well as isolated human neutrophils. In C. rodentium-induced colitis, NAM treatment resulted in markedly decreased systemic bacterial invasion, histological damage and increased fecal clearance of C. rodentium by up to 600-fold. In contrast, NAM had no effect when administered to neutrophil-depleted mice. Ex vivo stimulation of isolated human neutrophils, as well as murine and human whole blood with NAM led to increased clearance of C. rodentium and enhanced expression of antimicrobial peptides in neutrophils. Moreover, NAM treatment significantly ameliorated the course of DSS colitis, as assessed by body weight, histological damage and myeloperoxidase activity.
Pharmacological application of NAM mediates beneficial effects in bacterial and chemically induced colitis. Future studies are needed to explore the clinical potential of NAM in the context of intestinal bacterial infections and human inflammatory bowel disease (IBD).
在之前的研究中，我们可以证明维生素 B 烟酰胺（NAM）增强了中性粒细胞的抗菌活性。在这里，我们评估了 NAM 在两种实验性结肠炎模型中的作用。
通过口服感染柠檬酸杆菌或 DSS（葡聚糖硫酸钠）给药在 C57BL/6 小鼠中诱导结肠炎，并用 NAM 对动物进行全身治疗。在鼠和人全血以及分离的人中性粒细胞中评估了体外细菌清除率。在柠檬酸杆菌诱导的结肠炎中，NAM 治疗导致系统细菌侵袭显著减少、组织损伤减轻，柠檬酸杆菌的粪便清除率增加高达 600 倍。相比之下，当给予中性粒细胞耗竭的小鼠时，NAM 没有效果。用 NAM 体外刺激分离的人中性粒细胞以及鼠和人全血导致 C. rodentium 的清除率增加，并增强中性粒细胞中抗菌肽的表达。此外，NAM 治疗显著改善了 DSS 结肠炎的病程，通过体重、组织损伤和髓过氧化物酶活性来评估。
NAM 的药物应用介导了细菌和化学诱导的结肠炎的有益作用。需要进一步的研究来探索 NAM 在肠道细菌感染和人类炎症性肠病（IBD）背景下的临床潜力。
