Transdermal nicotine decreases mucosal IL-8 expression but has no effect on mucin gene expression in ulcerative colitis.
Our goal was to determine the effect of transdermal nicotine on cytokine and mucin gene transcription in ulcerative colitis (UC). Sixty-four nonsmoking patients with active UC were randomly assigned to transdermal nicotine (maximum dose 22 mg/day) or placebo for 4 weeks. Clinical assessment and colonic mucosal biopsies were obtained at entry and after 4 weeks. Inflammatory and immunoregulatory cytokines were assessed by qualitative reverse transcriptase-polymerase chain reaction (RT-PCR). Based on this initial screen. IL-8 mRNA levels were measured by RT-competitive PCR. MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, and MUC6 mRNA concentrations were measured by quantitative dot blot analysis. Cytokine mRNA expression, except for IL-8, was similar in all patients. IL-8 mRNA levels were significantly decreased in the colonic mucosa of nicotine-treated patients who improved (p = 0.04). IL-8 mRNA values were similar before and after treatment in nonresponding nicotine-treated patients and in all placebo-treated patients. Mucin gene expression was similar in all patient groups. Beneficial effects of transdermal nicotine in active UC may result from decrease of IL-8 expression at the transcriptional level. Transdermal nicotine has no effect on mucin gene transcription.
Louvet
B
B
Laboratoire de recherche sur les MICI (CRI 4U004B), Centre Hospitalier Universitaire (CHU), Lille, France.
Buisine
M P
MP
Desreumaux
P
P
Tremaine
W J
WJ
Aubert
J P
JP
Porchet
N
N
Capron
M
M
Cortot
A
A
Colombel
J F
JF
Sandborn
W J
WJ
D000279:Administration, Cutaneous; D000328:Adult; D015152:Blotting, Northern; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism*; D003106:Colon / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004311:Double-Blind Method; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D009077:Mucins / Q000096:biosynthesis* / Q000235:genetics; D009538:Nicotine / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D016209:Interleukin-8; D009077:Mucins; D012333:RNA, Messenger; D009538:Nicotine