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Gut 50:206-211 doi:10.1136/gut.50.2.206
  • Inflammation and inflammatory bowel disease

Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn's disease

  1. T ten Hove,
  2. C van Montfrans,
  3. M P Peppelenbosch,
  4. S J H van Deventer
  1. Academic Medical Centre University of Amsterdam, Department of Experimental Internal Medicine, Amsterdam, the Netherlands
  1. Correspondence to:
    T ten Hove, Academic Medical Centre, Department of Experimental Internal Medicine G2-105, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands;
    T.tenhove{at}amc.uva.nl
  • Accepted 3 July 2001

Abstract

Background and aims: Treatment with infliximab induces remission in about 70% of patients with steroid refractory Crohn's disease. Because Crohn's disease is considered to be mediated by uncontrolled activation of mucosal T lymphocytes, we hypothesised that infliximab could induce apoptosis of T lymphocytes.

Methods: Induction of apoptosis in vivo was studied in 10 patients with therapy refractory Crohn's disease. In vitro, resting or stimulated Jurkat T cells were incubated with infliximab.

Results: Infusion of infliximab (5 mg/kg) in steroid refractory patients with Crohn's disease induced a clinical response in 9/10 patients but did not influence expression of activation markers, homing receptors, memory cells, Fas expression, or Bax/Bcl-2 expression on peripheral blood T lymphocytes. In contrast, a significant increase in CD3 and TUNEL positive cells within colonic biopsies was detected 24 hours after infusion of infliximab, suggesting that infliximab stimulates apoptosis of activated T lymphocytes but not of resting T cells. To test this hypothesis, the effects of infliximab on Jurkat T cells were investigated. We observed that infliximab induced apoptosis and an increase in the Bax/Bcl-2 ratio of CD3/CD28 stimulated Jurkat T cells but not of unstimulated Jurkat cells.

Conclusions: Our data indicate that infliximab treatment causes a rapid and specific increase in apoptosis of T lymphocytes in the gut mucosa. These findings may explain the rapid and sustained therapeutic effects of infliximab in Crohn's disease.

Footnotes