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INFLAMMATION AND INFLAMMATORY BOWEL DISEASE |
Academic Medical Centre University of Amsterdam, Department of Experimental Internal Medicine, Amsterdam, the Netherlands
Correspondence to:
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
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.
Keywords: apoptosis; T lymphocytes; Crohn's disease; infliximab; tumour necrosis factor
Abbreviations: TNF-
, tumour necrosis factor ; CRP, C reactive protein; CDAI, Crohn's disease activity index; MFI, mean fluorescence intensity; IFN-
, interferon
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