Cytokine profiles differ in newly recruited and resident subsets of mucosal macrophages from inflammatory bowel disease.
OBJECTIVE
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.
Rugtveit
J
J
Laboratory for Immunohistochemistry and Immunopathology, University of Oslo, The National Hospital, Rikshospitalet, Norway.
Nilsen
E M
EM
Bakka
A
A
Carlsen
H
H
Brandtzaeg
P
P
Scott
H
H
D000328:Adult; D000368:Aged; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D016130:Immunophenotyping; D015212:Inflammatory Bowel Diseases / Q000378:metabolism* / Q000473:pathology; D016753:Interleukin-10 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000145:classification / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism
D016207:Cytokines; D018124:Receptors, Tumor Necrosis Factor; D016753:Interleukin-10