Article Text
Abstract
Background: Interleukin 10 (IL-10) exerts anti-inflammatory actions by counteracting many biological effects of interferon γ (IFN-γ).
Aims: To investigate this in humans, we studied the effects of human recombinant IL-10 administration on IFN-γ production by patient leucocytes. Furthermore, we assessed the IFN-γ 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-γ 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 μg/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 μg/kg IL-10 resulted in a significant increase in PHA induced IFN-γ production.
Conclusions: High doses of IL-10 upregulate the production of IFN-γ 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.
- inflammatory bowel disease
- inflammation
- interleukin 10
- neopterin
- interferon γ
- CACD, chronic active Crohn's disease
- CD, Crohn's disease
- CDAI, Crohn's disease activity index
- GVHD, graft versus host disease
- IFN-γ, interferon γ
- IL, interleukin
- rHuIL-10, recombinant human IL-10
- iNOS, inducible nitric oxide synthase
- LPS, lipopolysaccharide
- MCD, mild to moderately active CD
- NO, nitric oxide
- PHA, phytohaemagglutinin
- Th, T helper cells
- TNF-α, tumour necrosis factor α
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- CACD, chronic active Crohn's disease
- CD, Crohn's disease
- CDAI, Crohn's disease activity index
- GVHD, graft versus host disease
- IFN-γ, interferon γ
- IL, interleukin
- rHuIL-10, recombinant human IL-10
- iNOS, inducible nitric oxide synthase
- LPS, lipopolysaccharide
- MCD, mild to moderately active CD
- NO, nitric oxide
- PHA, phytohaemagglutinin
- Th, T helper cells
- TNF-α, tumour necrosis factor α