Mechanisms of Disease: Nicotine -- A Review of its Actions in the Context of Gastrointestinal Disease

Gareth AO Thomas; John Rhodes; John R Ingram

Disclosures

Nat Clin Pract Gastroenterol Hepatol. 2005;2(11):536-544. 

In This Article

Conclusions

The diverse epidemiologic links between smoking and certain gastrointestinal conditions are of interest, and could hold the key to a better understanding of their etiology. The obvious example is the 'polarizing effect' of smoking status in patients with ulcerative colitis and Crohn's disease. The relevant mechanisms that account for these associations have been difficult to identify, because smoking and nicotine have so many pharmacologic effects on the central nervous system, immune system, and the gastrointestinal tract; however, it is likely that nicotine, through its many 'positive' and 'negative' biological effects, plays a key role in this conundrum.

It is possible to speculate that the disease phenotype of an individual is influenced by factors such as genetic susceptibility, and that subsequent exposure to nicotine modifies this. For example, an individual susceptible to developing ulcerative colitis, who smokes, might reduce their chance of developing the disease through the effects of nicotine on the immune system and/or colonic motility. By contrast, an individual at risk of Crohn's disease, who smokes, might increase their chance of developing the disease because of the effects of smoking or nicotine on macrophage function and/or the microvasculature (Figure 1). The beneficial effects of nicotine or smoking in ulcerative colitis, might or might not be due to the same mechanisms that are detrimental in Crohn's disease. Either way, these probably influence other underlying abnormalities to produce the disease phenotype. For example, the immunosuppressive effect of smoking or nicotine on macrophage function in Crohn's disease might be important in exacerbating any underlying deficiency in the host response to luminal bacteria. By contrast, although the role of luminal bacteria in ulcerative colitis might be important, the host response might not be impaired, and the immunosuppressive effect on macrophages need not be detrimental, and might even be beneficial. It is also likely that the effects of nicotine that are 'positive' in one site of the gastrointestinal tract might be 'negative' in another. For example, the effect of nicotine on decreasing the motility of the colon might be beneficial, in ulcerative colitis; and yet the same effect in the esophagus might be detrimental, in GERD. Further work exploring the role of nicotine in gastrointestinal disease is required, in the hope that it will lead to a better understanding of disease mechanisms, and possibly improve therapeutic alternatives.

Proposed mechanism by which nicotine and smoking might influence the risk of a susceptible individual towards developing either ulcerative colitis or Crohn's disease. CARD15, caspase recruitment domain family, member 15; nAChR, nicotinic acetylcholine receptor; NO, nitric oxide; TNF, tumor necrosis factor.


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