Cytokine profiles differ in newly recruited and resident subsets of mucosal macrophages from inflammatory bowel disease

Gastroenterology. 1997 May;112(5):1493-505. doi: 10.1016/s0016-5085(97)70030-1.

Abstract

Background & aims: Most macrophages in the normal intestinal mucosa have a mature phenotype. In inflammatory bowel disease (IBD), a monocyte-like subset (CD14+ L1+) accumulates. The aim of this study was to characterize its potential with regard to cytokines.

Methods: Lamina propria mononuclear cells were adherence-separated, with or without depletion of CD14+ cells, and production of cytokines was investigated by bioassay, enzyme-linked immunosorbent assay, or immunocytochemistry.

Results: Tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), and IL-1 receptor antagonist were found mainly in cells positive for myelomonocytic L1. In undepleted IBD cultures, TNF-alpha, IL-1alpha and beta, and IL-10 were markedly up-regulated by pokeweed mitogen stimulation; IL-1alpha and beta and IL-10 were also up-regulated by stimulation of interferon gamma and lipopolysaccharide in combination. The latter stimulation had no effect on normal control or CD14-depleted IBD cultures. Indomethacin caused a marked increase of TNF-alpha, particularly in undepleted IBD cultures, whereas IL-10 and IL-4 decreased TNF-alpha and IL-1beta in both CD14+ and CD14 macrophages.

Conclusions: In IBD mucosa, macrophages with a monocyte-like phenotype are primed for production of TNF-alpha and IL-1alpha/beta and may therefore be of significant pathogenic importance [corrected]. However, this CD14+ subset, as well as the mucosal resident macrophages, have preserved responsiveness to several down-regulatory factors such as the macrophage deactivators IL-10 and IL-4.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Aged
  • Cytokines / metabolism*
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Immunophenotyping
  • Inflammatory Bowel Diseases / metabolism*
  • Inflammatory Bowel Diseases / pathology
  • Interleukin-10 / biosynthesis
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology
  • Macrophages / classification
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Male
  • Middle Aged
  • Receptors, Tumor Necrosis Factor / metabolism

Substances

  • Cytokines
  • Receptors, Tumor Necrosis Factor
  • Interleukin-10