In-vivo effect of nicotine on cytokine production by human non-adherent mononuclear cells.
OBJECTIVE
Ulcerative colitis (UC) is predominantly a disease of non-smokers and treatment with transdermal nicotine improves symptoms in UC patients, whereas smoking seems to have a deleterious effect in patients with Crohn's disease (CD). In CD the cytokine profile is of a dominant TH1 (T helper 1) pattern whereas in UC the TH2 pattern predominates. To find an explanation for the beneficial effect of nicotine in UC and the deteriorative effect in CD we studied the in-vivo effect of nicotine on the interleukin 2 (IL-2), IL-10 and tumour necrosis factor alpha (TNF alpha) production by human cells.


METHODS
Eleven healthy male non-smokers were included in this study. The volunteers applied nicotine patches with a regulated release of 5 mg (day 1 and 2), 10 mg (day 3 and 4) and 15 mg (day 5, 6 and 7) nicotine per day.


METHODS
Heart rate and blood pressure were recorded, nicotine and cotinine concentrations in plasma measured before and after 2, 4 and 7 days of treatment. Non-adherent mononuclear cells (NAC) were isolated from peripheral blood obtained from the subjects before and after 7 days of treatment. The NAC were cultured in the absence or presence of phytohemagglutinin for 48 h. Total amount of IL-2, IL-10 and TNF alpha formed were measured in the supernatants using specific ELISAs.


RESULTS
Treatment with nicotine caused a significant inhibition of IL-10 production by NAC. In contrast, nicotine patch treatment had no effect on the production of IL-2 and TNF alpha.


CONCLUSIONS
Nicotine in vivo has an inhibitory effect on TH2 cell function as measured by inhibition of IL-10 production, but does not appear to have any effect on TH1 cell function.
Madretsma
S
S
Department of Pharmacology, Erasmus University, Rotterdam, The Netherlands.
Wolters
L M
LM
van Dijk
J P
JP
Tak
C J
CJ
Feyerabend
C
C
Wilson
J H
JH
Zijlstra
F J
FJ
D000328:Adult; D018929:Cell Culture Techniques; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000503:physiopathology; D003424:Crohn Disease / Q000188:drug therapy / Q000503:physiopathology; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000378:metabolism / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009538:Nicotine