title: Rectal nitric oxide as biomarker in the treatment of inflammatory bowel disease: responders versus nonresponders.
abstract: 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.
authors.affiliation: Department of Gastroenterology and Hepatology, Karolinska University Hospital, Site Solna, Stockholm, Sweden. tryggve.ljung@hotmail.com
authors.forename: Tryggve
authors.initials: T
authors.lastname: Ljung
authors.forename: Sofie
authors.initials: S
authors.lastname: Lundberg
authors.forename: Mark
authors.initials: M
authors.lastname: Varsanyi
authors.forename: Catharina
authors.initials: C
authors.lastname: Johansson
authors.forename: Peter T
authors.initials: PT
authors.lastname: Schmidt
authors.forename: Max
authors.initials: M
authors.lastname: Herulf
authors.forename: Jon O
authors.initials: JO
authors.lastname: Lundberg
authors.forename: Per M
authors.initials: PM
authors.lastname: Hellstrom
mesh_terms: 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
chemical_list: 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