title: Treatment of Crohn's disease with recombinant human interleukin 10 induces the proinflammatory cytokine interferon gamma.
abstract: BACKGROUND
  Interleukin 10 (IL-10) exerts anti-inflammatory actions by counteracting many biological effects of interferon gamma (IFN-gamma).
  
  
  OBJECTIVE
  To investigate this in humans, we studied the effects of human recombinant IL-10 administration on IFN-gamma production by patient leucocytes. Furthermore, we assessed the IFN-gamma inducible molecule neopterin and nitrite/nitrate serum levels, which are indicative of endogenous nitric oxide formation.
  
  
  METHODS
  As part of two placebo controlled double blind studies, we analysed patients with chronic active Crohn's disease (CACD) who received either subcutaneous recombinant human IL-10 (n=44) or placebo (n=10) daily for 28 days, and patients with mild to moderate Crohn's disease (MCD) treated with either subcutaneous IL-10 (n=52) or placebo (n=16) daily for 28 days. Neopterin and nitrite/nitrate concentrations were measured in serum, and ex vivo IFN-gamma formation by lipopolysaccharide or phytohaemagglutinin (PHA) stimulated whole blood cells were investigated before, during, and after IL-10 therapy.
  
  
  RESULTS
  In patients with CACD, the highest dose of 20 microg/kg IL-10 caused a significant increase in serum neopterin on days +15 and +29 of therapy compared with pretreatment levels. No changes were observed for nitrite/nitrate levels under either condition. In MCD, treatment with 20 microg/kg IL-10 resulted in a significant increase in PHA induced IFN-gamma production.
  
  
  CONCLUSIONS
  High doses of IL-10 upregulate the production of IFN-gamma and neopterin. This phenomenon may be responsible for the lack of efficacy of high doses of IL-10 in the treatment of CACD and MCD.
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, University Hospital Innsbruck, Austria. Herbert.Tilg@uibk.ac.at
authors.forename: H
authors.initials: H
authors.lastname: Tilg
authors.forename: C
authors.initials: C
authors.lastname: van Montfrans
authors.forename: A
authors.initials: A
authors.lastname: van den Ende
authors.forename: A
authors.initials: A
authors.lastname: Kaser
authors.forename: S J H
authors.initials: SJ
authors.lastname: van Deventer
authors.forename: S
authors.initials: S
authors.lastname: Schreiber
authors.forename: M
authors.initials: M
authors.lastname: Gregor
authors.forename: O
authors.initials: O
authors.lastname: Ludwiczek
authors.forename: P
authors.initials: P
authors.lastname: Rutgeerts
authors.forename: C
authors.initials: C
authors.lastname: Gasche
authors.forename: J C
authors.initials: JC
authors.lastname: Koningsberger
authors.forename: L
authors.initials: L
authors.lastname: Abreu
authors.forename: I
authors.initials: I
authors.lastname: Kuhn
authors.forename: M
authors.initials: M
authors.lastname: Cohard
authors.forename: A
authors.initials: A
authors.lastname: LeBeaut
authors.forename: P
authors.initials: P
authors.lastname: Grint
authors.forename: G
authors.initials: G
authors.lastname: Weiss
mesh_terms: D000279:Administration, Cutaneous; D002908:Chronic Disease; D003092:Colitis / Q000188:drug therapy / Q000378:metabolism; D003424:Crohn Disease / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D004351:Drug Resistance; D005500:Follow-Up Studies; D006801:Humans; D007079:Ileitis / Q000188:drug therapy / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism; D019798:Neopterin / Q000097:blood; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes
chemical_list: D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D010835:Phytohemagglutinins; D016753:Interleukin-10; D019798:Neopterin; D007371:Interferon-gamma