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

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 1 beta (IL-1 beta), and IL-1 receptor antagonist were found mainly in cells positive for myelomonocytic L1. In undepleted IBD cultures, TNF-alpha, IL-1 alpha and beta, and IL-10 were markedly up-regulated by pokeweed mitogen stimulation; IL-1 alpha 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-1 beta in both CD14(+) and CD14 macrophages. Conclusions: In IBD mucosa, macrophages with a monocyte-like phenotype are primed for production of TNF-alpha; IL-1 alpha and beta may therefore have significant pathogenic importance. 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.