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

Gut. 2002 Feb;50(2):206-11. doi: 10.1136/gut.50.2.206.

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.

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use*
  • Apoptosis*
  • Biomarkers / analysis
  • CD28 Antigens / metabolism
  • CD3 Complex / metabolism
  • Crohn Disease / drug therapy*
  • Crohn Disease / metabolism
  • Crohn Disease / pathology
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Infliximab
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Jurkat Cells
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / pathology
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Biomarkers
  • CD28 Antigens
  • CD3 Complex
  • Gastrointestinal Agents
  • Infliximab