Hypothesis about mechanisms through which nicotine might exert its effect on the interdependence of inflammation and gut barrier function in ulcerative colitis.
Ulcerative colitis (UC) is characterized by impairment of the epithelial barrier and the formation of ulcer-type lesions, which result in local leaks and generalized alterations of mucosal tight junctions. Ultimately, this results in increased basal permeability. Although disruption of the epithelial barrier in the gut is a hallmark of inflammatory bowel disease and intestinal infections, it remains unclear whether barrier breakdown is an initiating event of UC or rather a consequence of an underlying inflammation, evidenced by increased production of proinflammatory cytokines. UC is less common in smokers, suggesting that the nicotine in cigarettes may ameliorate disease severity. The mechanism behind this therapeutic effect is still not fully understood, and indeed it remains unclear if nicotine is the true protective agent in cigarettes. Nicotine is metabolized in the body into a variety of metabolites and can also be degraded to form various breakdown products. It is possible these metabolites or degradation products may be the true protective or curative agents. A greater understanding of the pharmacodynamics and kinetics of nicotine in relation to the immune system and enhanced knowledge of gut permeability defects in UC are required to establish the exact protective nature of nicotine and its metabolites in UC. This review suggests possible hypotheses for the protective mechanism of nicotine in UC, highlighting the relationship between gut permeability and inflammation, and indicates where in the pathogenesis of the disease nicotine may mediate its effect.
McGilligan
Victoria E
VE
Northern Ireland Centre for Food and Health (NICHE), Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, United Kingdom. vmcgilligan@yahoo.co.uk
Wallace
Julie M W
JM
Heavey
Patricia M
PM
Ridley
Diana L
DL
Rowland
Ian R
IR
D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D003106:Colon / Q000473:pathology; D016207:Cytokines / Q000502:physiology; D006801:Humans; D007249:Inflammation; D007422:Intestines / Q000503:physiopathology; D009538:Nicotine / Q000494:pharmacology* / Q000627:therapeutic use; D010539:Permeability; D012907:Smoking
D016207:Cytokines; D009538:Nicotine