IN-VIVO EFFECT OF NICOTINE ON CYTOKINE PRODUCTION BY HUMAN NONADHERENT MONONUCLEAR-CELLS

Objective: Ulcerative colitis (UC) is predominantly a disease of non-s mokers and treatment with transdermal nicotine improves symptoms in UC patients, whereas smoking seems to have a deleterious effect in patie nts with Crohn's disease (CD). In CD the cytokine profile is of a domi nant T(H)1 (T helper 1) pattern whereas in UC the T(H)2 pattern predom inates. To find an explanation for the beneficial effect of nicotine i n 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 fac tor alpha (TNF alpha) production by human cells. Design: Eleven health y 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 m g (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 con centrations in plasma measured before and after 2, 4 and 7 days of tre atment. Non-adherent mononuclear cells (NAG) were isolated from periph eral blood obtained from the subjects before and after 7 days of treat ment. The NAC were cultured in the absence or presence of phytohemaggl utinin for 48 h. Total amount of IL-2, IL-10 and TNF alpha formed were measured in the supernatants using specific ELISAs. Results: Treatmen t with nicotine caused a significant inhibition of IL-10 production by NAG. In contrast, nicotine patch treatment had no effect on the produ ction of IL-2 and TNF alpha. Conclusions: Nicotine in vivo has an inhi bitory effect on T(H)2 cell function as measured by inhibition of IL-1 0 production, but does not appear to have any effect on T(H)1 cell fun ction.