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 ha ve 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 p ropria mononuclear cells were adherence-separated, with or without dep letion 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-regul ated by stimulation of interferon gamma and lipopolysaccharide in comb ination, The latter stimulation had no effect on normal control or CD1 4-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 macrophage s. Conclusions: In IBD mucosa, macrophages with a monocyte-like phenot ype are primed for production of TNF-alpha; IL-1 alpha and beta may th erefore have significant pathogenic importance. However, this CD14(+) subset, as well as the mucosal resident macrophages, have preserved re sponsiveness to several down-regulatory factors such as the macrophage deactivators IL-10 and IL-4.