title: Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease. Crohn's Disease IL-10 Cooperative Study Group.
abstract: OBJECTIVE
  Interleukin (IL)-10 is a cytokine with potent anti-inflammatory properties. We investigated the safety and efficacy of different doses of human recombinant (rhu)IL-10 in patients with Crohn's disease (CD).
  
  
  METHODS
  A prospective, multicenter, double-blind, placebo-controlled study was conducted in 329 therapy-refractory patients with CD. Clinical improvement was defined by a reduction of the Crohn's Disease Activity Index (CDAI) by 100 points or more and clinical remission by a decrease of the CDAI to <150 points. At selected centers, patients underwent ileocolonoscopies and activation of the nuclear factor-kappa B (NF-kappa B) system was assessed in biopsy specimens.
  
  
  RESULTS
  Subcutaneous treatment with rhuIL-10 over 28 days induced a fully reversible, dose-dependent decrease in hemoglobin and thrombocyte counts but no clinically significant side effects. No differences in the induction of remission were observed between rhuIL-10 groups (1 microg, 18% [9.6-29.2]; 4 microg, 20% [11.3-32.2]; 8 microg, 20% [11.1-31.8]; 20 microg, 28% [18-40.7]; and placebo, 18% [9.6-29.6]). Clinical improvement was observed in 46% (33.7-59) in the 8-microg/kg rhuIL-10 group in comparison with 27% (17-39.6) in patients taking placebo. Responders to rhuIL-10 showed inhibition of NF-kappaB p65 activation in contrast to nonresponders.
  
  
  CONCLUSIONS
  Up to 8 microg/kg of rhuIL-10 was well tolerated. A tendency toward clinical improvement but not remission was observed in the 8-microg/kg dose group. Further studies should delineate which subgroups of patients with CD benefit from rhuIL-10 therapy.
authors: Charité University Hospital, Fourth Medical Department, Humboldt University, Berlin, Germany. s.schreiber@mucosa.de
authors: S
authors: S
authors: Schreiber
authors: R N
authors: RN
authors: Fedorak
authors: O H
authors: OH
authors: Nielsen
authors: G
authors: G
authors: Wild
authors: C N
authors: CN
authors: Williams
authors: S
authors: S
authors: Nikolaus
authors: M
authors: M
authors: Jacyna
authors: B A
authors: BA
authors: Lashner
authors: A
authors: A
authors: Gangl
authors: P
authors: P
authors: Rutgeerts
authors: K
authors: K
authors: Isaacs
authors: S J
authors: SJ
authors: van Deventer
authors: J C
authors: JC
authors: Koningsberger
authors: M
authors: M
authors: Cohard
authors: A
authors: A
authors: LeBeaut
authors: S B
authors: SB
authors: Hanauer
mesh_terms: D000328:Adult; D002908:Chronic Disease; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004351:Drug Resistance; D016145:Endoscopy, Digestive System; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000502:physiology; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D010352:Patient Dropouts; D011446:Prospective Studies; D011788:Quality of Life; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012074:Remission Induction; D019233:Retreatment; D012449:Safety; D012720:Severity of Illness Index; D013256:Steroids / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D020672:I-kappa B Proteins; D011994:Recombinant Proteins; D013256:Steroids; D016753:Interleukin-10