Transdermal nicotine inhibits interleukin 2 synthesis by mononuclear cells derived from healthy volunteers.
BACKGROUND
Smoking has either a beneficial or harmful effect on the course and recurrence of ulcerative colitis (UC) and Crohn's disease respectively. Transdermal application of nicotine had similar effects in UC and therefore was considered to be an effective basic drug that could be further developed in the search for new compounds in the treatment of acute exacerbations of corticosteroid-resistant UC. To clarify the hypothesis that nicotine exerts its anti-inflammatory effect in UC through selective inhibition of T-cell-derived cytokine synthesis, we studied in vivo effects of nicotine on cytokine production by human non-adherent mononuclear cells isolated from peripheral blood in a randomized, double-blind, placebo-controlled trial.


METHODS
Healthy non-smoking volunteers applied for 2 weeks of nicotine patches (n = 12) with incremental doses of nicotine during the first week to achieve a maintenance dose of 15 mg per day, or placebo (n = 12). Blood was obtained before treatment and 1, 2, 3 and 6 weeks after the start of treatment. Cells were cultured in the absence or presence of phytohaemagglutinin for 48 h, and total amounts of interleukin 2 (IL-2), IL-4, IL-10, IL-13, interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) were measured.


RESULTS
Transdermal nicotine caused a significant inhibition of IL-2 after 2 weeks' treatment compared with the placebo group. In addition, a diminished production of IL-10 and TNF-alpha in comparison with day 0 was observed.


CONCLUSIONS
The beneficial effect of transdermal nicotine in ulcerative colitis may be mediated by a selective inhibition of the IL-2 production by mucosal mononuclear cells, which could result in diminished cell proliferation and consequently a reduction in the inflammatory process.
Department of Pharmacology, Erasmus University, Rotterdam, The Netherlands. vandijk@FARMA.FGG.EUR.NL
A P
AP
van Dijk
M A
MA
Meijssen
A J
AJ
Brouwer
W C
WC
Hop
J D
JD
van Bergeijk
C
C
Feyerabend
J H
JH
Wilson
F J
FJ
Zijlstra
D000279:Administration, Cutaneous; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D003367:Cotinine / Q000097:blood; D015232:Dinoprostone / Q000097:blood; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood; D018793:Interleukin-13 / Q000096:biosynthesis / Q000097:blood; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D007975:Leukotriene B4 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage* / Q000097:blood; D018722:Nicotinic Agonists / Q000008:administration & dosage* / Q000097:blood; D010835:Phytohemagglutinins / Q000494:pharmacology; D016540:Smoking Cessation; D013929:Thromboxane B2 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D018793:Interleukin-13; D007376:Interleukin-2; D018722:Nicotinic Agonists; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007975:Leukotriene B4; D015847:Interleukin-4; D013929:Thromboxane B2; D009538:Nicotine; D007371:Interferon-gamma; D003367:Cotinine; D015232:Dinoprostone