Chronic nicotine administration differentially alters jejunal and colonic inflammation in interleukin-10 deficient mice.
BACKGROUND
Cigarette smoking alters the course of inflammatory bowel disease, is associated with protection against ulcerative colitis, but aggravates or has no effect on Crohn's disease. While the aetiology of this discrepancy remains unclear, differences between location of involvement in ulcerative colitis and Crohn's disease have not been examined in these studies.


OBJECTIVE
To examine the effects of nicotine administration on the course of jejunitis and colitis in interleukin-10 deficient mice.


METHODS
Male C57/BL10 IL-10 -/- and wild type mice were given nicotine (12.5 microg/ml) in their drinking water at age 12-14 weeks when they had developed clinical signs of inflammatory bowel disease. Gender and age matched control mice received tap water alone. All mice were killed after 2 weeks of treatment. Whole tissue sections of jejunum, proximal and distal colon were separated and examined by macroscopic and histological score. Northern blots were examined for somatostatin, intestinal trefoil factor and mucin-2.


RESULTS
At 14-16 weeks, when the mice were killed, IL-10 -/- untreated control mice developed jejunitis (macroscopic score 1.4 +/- 0.5, microscopic score 2.0 +/- 0.2) and colitis (2.0 +/- 0.2 and 5.9 +/- 0.9, respectively). IL-10 -/- mice treated for 2 weeks with nicotine had significantly reduced colonic scores (1.4 +/- 0.6 and 2.2 +/- 0.15, respectively). In contrast, the jejunum was more severely damaged (2.6 +/- 0.4 and 4.0 +/- 0.3; P = 0.01, respectively). Nicotine significantly increased both somatostatin and intestinal trefoil factor mRNA expression in the colon but not in the jejunum; no effect was noted on mucin-2 or beta-actin mRNA expression.


CONCLUSIONS
(1) Two weeks of nicotine administration leads to contrasting effects on jejunal and colonic inflammation in IL-10 -/- mice. (2) Nicotine ameliorated inflammation in the colon, which was associated with enhanced expression of two protective peptides.
Eliakim
Rami
R
Department of Medicine, Rambam Medical Center, Haifa, Israel. r_eliakim@rambam.health.gov.il
Fan
Qiu Xiang
QX
Babyatsky
Mark W
MW
D000199:Actins / Q000032:analysis; D000818:Animals; D003092:Colitis / Q000517:prevention & control*; D006133:Growth Substances / Q000032:analysis; D007249:Inflammation / Q000517:prevention & control*; D016753:Interleukin-10 / Q000172:deficiency*; D007579:Jejunal Diseases / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009077:Mucins / Q000032:analysis; D009124:Muscle Proteins; D009479:Neuropeptides; D009538:Nicotine / Q000008:administration & dosage*; D010455:Peptides / Q000032:analysis; D013004:Somatostatin / Q000032:analysis; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3
D000199:Actins; D006133:Growth Substances; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides; C099037:TFF3 protein, rat; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D016753:Interleukin-10; D013004:Somatostatin; D009538:Nicotine