Decreased lamina propria effector cell responsiveness to interleukin-10 in ileal Crohn's disease

Clin Immunol. 2002 Jan;102(1):68-76. doi: 10.1006/clim.2001.5149.

Abstract

We investigated whether a lack of IL-10 production or responsiveness could be involved in Crohn's disease pathogenesis. Lamina propria mononuclear cells, isolated from the ilea of Crohn's disease patients (n = 16) and controls (n = 13), were activated with anti-CD3 mAb in the presence of CD80 transfectants or LPS +/- IFN-gamma. No evidence for deficient IL-10 production by either T cells or macrophages in Crohn's disease was found. However, the efficacy of rhIL-10 to down-regulate IFN-gamma and especially TNF production in cell cultures from the involved tissues of Crohn's disease patients was poor, and the use of an anti-IL-10R mAb even provided evidence for proinflammatory effects of IL-10. This lack of IL-10 effect possibly results from IL-12 activity. We conclude that IL-10 exhibits poor anti- and even potential proinflammatory effects on ileal Crohn's disease lamina propria. These data might explain the lack of therapeutic efficacy when IL-10 is given to Crohn's disease patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / metabolism*
  • Cells, Cultured
  • Crohn Disease / etiology
  • Crohn Disease / immunology*
  • Drug Interactions
  • Humans
  • Ileal Diseases / etiology
  • Ileal Diseases / immunology*
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism*
  • Interleukin-12 / metabolism
  • Interleukin-12 / pharmacology
  • Interleukin-2 / pharmacology
  • Interleukin-4 / pharmacology
  • Macrophages / immunology
  • Receptors, Interleukin / metabolism
  • Receptors, Interleukin-10
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-2
  • Receptors, Interleukin
  • Receptors, Interleukin-10
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma