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Nicotinamide treatment ameliorates the course of experimental colitis mediated by enhanced neutrophil‐specific antibacterial clearance
Author(s) -
Bettenworth Dominik,
Nowacki Tobias M.,
Ross Matthias,
Kyme Pierre,
Schwammbach Daniela,
Kerstiens Linda,
Thoennissen Gabriela B.,
Bokemeyer Carsten,
Hengst Karin,
Berdel Wolfgang E.,
Heidemann Jan,
Thoennissen Nils H.
Publication year - 2014
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201300818
Subject(s) - colitis , citrobacter rodentium , ex vivo , nicotinamide , in vivo , immunology , inflammatory bowel disease , antimicrobial , context (archaeology) , medicine , microbiology and biotechnology , pharmacology , biology , disease , biochemistry , paleontology , enzyme
Scope 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. Methods and Results 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. Conclusion 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).