Budesonide treatment and expression of inducible nitric oxide synthase mRNA in colonic mucosa in collagenous colitis.
OBJECTIVE
In collagenous colitis, the production of nitric oxide in the colon is found to be 50 to 100-fold higher than in healthy controls. The role of nitric oxide in collagenous colitis is debated and it has been suggested that nitric oxide has a causative role in diarrhoea. The aim of this study was to examine the possible effect of budesonide treatment on the level of inducible nitric oxide synthase mRNA.


METHODS
In 20 patients with collagenous colitis, clinical activity was assessed by registration of the daily stool frequency and stool weight. Sigmoidoscopy was performed and biopsies for histological examination and one biopsy for determination of inducible nitric oxide synthase mRNA was obtained in 16 patients.


RESULTS
Budesonide treatment was followed by a significant reduction of inducible nitric oxide synthase mRNA (P<0.01) whereas no change was observed after placebo treatment. Significant correlations between inducible nitric oxide synthase mRNA and the grade of inflammation (rho=0.47; P<0.01), the daily stool weight (rho=0.51; P<0.005) and the daily stool frequency (rho=0.49; P<0.005) were observed. No significant association was observed between inducible nitric oxide synthase mRNA and the thickness of the collagen layer.


CONCLUSIONS
In patients with collagenous colitis, treatment with budesonide results in a reduction of inducible nitric oxide synthase mRNA. The level of inducible nitric oxide synthase mRNA in colonic mucosa correlates with the inflammatory and clinical activity. The results support that nitric oxide is a central factor in the pathogenesis of collagenous colitis.
Bonderup
Ole K
OK
Department of Medicine, Randers Hospital, Randers, Denmark. obo@rc.aaa.dk
Hansen
Jesper B
JB
Madsen
Poul
P
Vestergaard
Vibeke
V
Fallingborg
Jan
J
Teglbjaerg
Peter S
PS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D019819:Budesonide / Q000627:therapeutic use*; D046729:Colitis, Collagenous / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D003106:Colon / Q000201:enzymology; D004311:Double-Blind Method; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000473:pathology; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012720:Severity of Illness Index
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D012333:RNA, Messenger; D019819:Budesonide; D052247:Nitric Oxide Synthase Type II