Nicotinamide treatment ameliorates the course of experimental colitis mediated by enhanced neutrophil-specific antibacterial clearance.
METHODS
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.


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.


CONCLUSIONS
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).
Department of Medicine B, University of Münster, Münster, Germany.
Dominik
D
Bettenworth
Tobias M
TM
Nowacki
Matthias
M
Ross
Pierre
P
Kyme
Daniela
D
Schwammbach
Linda
L
Kerstiens
Gabriela B
GB
Thoennissen
Carsten
C
Bokemeyer
Karin
K
Hengst
Wolfgang E
WE
Berdel
Jan
J
Heidemann
Nils H
NH
Thoennissen
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D044082:Citrobacter rodentium / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004756:Enterobacteriaceae Infections / Q000188:drug therapy; D005243:Feces / Q000382:microbiology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007422:Intestines / Q000187:drug effects / Q000382:microbiology; D039841:Leukocyte L1 Antigen Complex / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D050296:Microbial Viability / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D022762:CCAAT-Enhancer-Binding Proteins; D039841:Leukocyte L1 Antigen Complex; C070790:CEBPE protein, human; D009536:Niacinamide; D016264:Dextran Sulfate
Bacterial killing; Colitis; Inflammation; Nicotinamide; Vitamin B3