Treatment of Crohn's disease with recombinant human interleukin 10 induces the proinflammatory cytokine interferon gamma

Gut. 2002 Feb;50(2):191-5. doi: 10.1136/gut.50.2.191.


Background: Interleukin 10 (IL-10) exerts anti-inflammatory actions by counteracting many biological effects of interferon gamma (IFN-gamma).

Aims: 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Chronic Disease
  • Colitis / drug therapy
  • Colitis / metabolism
  • Crohn Disease / drug therapy*
  • Crohn Disease / metabolism
  • Double-Blind Method
  • Drug Resistance
  • Follow-Up Studies
  • Humans
  • Ileitis / drug therapy
  • Ileitis / metabolism
  • Interferon-gamma / biosynthesis*
  • Interleukin-10 / therapeutic use*
  • Lipopolysaccharides / pharmacology
  • Monocytes / metabolism
  • Neopterin / blood
  • Nitrates / blood
  • Nitrites / blood
  • Phytohemagglutinins / pharmacology
  • T-Lymphocytes


  • Lipopolysaccharides
  • Nitrates
  • Nitrites
  • Phytohemagglutinins
  • Interleukin-10
  • Neopterin
  • Interferon-gamma