Rectal nitric oxide as biomarker in the treatment of inflammatory bowel disease: responders versus nonresponders.
OBJECTIVE
To explore rectal nitric oxide (NO) as biomarker of treatment response in ulcerative colitis (UC) and Crohn's disease (CD), and examine relationships between rectal NO, mucosal expression of NO synthases (NOS), and pro-inflammatory cytokines.


METHODS
Twenty-two patients with UC and 24 with CD were monitored during steroid treatment. Rectal NO levels were measured and clinical activities were assessed on days 1, 3, 7 and 28. Mucosal presence of NOS and pro-inflammatory cytokines were analyzed by immunohistochemistry and RT-PCR.


RESULTS
Active UC and CD displayed markedly increased rectal NO levels (10950 +/- 7610 and 5040 +/- 1280 parts per billion (ppb), respectively) as compared with the controls (154 +/- 71 ppb, P < 0.001). Rectal NO correlated weakly with disease activity in both UC and CD (r = 0.34 for UC and r = 0.48 for CD, P < 0.01). In 12 patients, a steroid-refractory course led to colectomy. These patients had only slightly increased NO levels (UC: 620 +/- 270 ppb; CD: 1260 +/- 550 ppb) compared to those with a therapeutic response (UC: 18860 +/- 530 ppb, P < 0.001; CD: 10060 +/- 3200 ppb, P < 0.05).


CONCLUSIONS
Rectal NO level is a useful biomarker of treatment response in IBD as low NO levels predicts a poor clinical response to steroid treatment.
Ljung
Tryggve
T
Department of Gastroenterology and Hepatology, Karolinska University Hospital, Site Solna, Stockholm, Sweden. tryggve.ljung@hotmail.com
Lundberg
Sofie
S
Varsanyi
Mark
M
Johansson
Catharina
C
Schmidt
Peter T
PT
Herulf
Max
M
Lundberg
Jon O
JO
Hellstrom
Per M
PM
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D003424:Crohn Disease / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D004351:Drug Resistance; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000032:analysis / Q000502:physiology; D007375:Interleukin-1 / Q000032:analysis / Q000502:physiology; D007413:Intestinal Mucosa / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000201:enzymology; D009569:Nitric Oxide / Q000032:analysis* / Q000502:physiology; D052248:Nitric Oxide Synthase Type I / Q000032:analysis / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000032:analysis / Q000502:physiology; D011237:Predictive Value of Tests; D012007:Rectum / Q000737:chemistry*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000502:physiology
D015415:Biomarkers; D005938:Glucocorticoids; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III