title: Regulatory effects of IL-13 on synovial fluid macrophages and blood monocytes from patients with inflammatory arthritis.
abstract: Activated macrophages are central to the destructive processes of chronic inflammatory arthritis. In this study, it was hypothesized that IL-13, a product predominantly of 'Th2-type' lymphocytes, may be used therapeutically to down-regulate monocyte/macrophage activities at sites of chronic inflammation. Synovial fluid mononuclear cells were isolated from 12 patients with chronic inflammatory arthritis. Peripheral blood mononuclear cells (PBMC) were isolated at the same time as synovial fluid cells from all 12 patients. IL-13 significantly inhibited lipopolysaccharide (LPS)-induced tumour necrosis factor-alpha (TNF-alpha) production by mononuclear cells from peripheral blood, but not synovial fluid. In contrast, IL-13 inhibited LPS-induced IL-1 beta production by all cells, and as a positive response to IL-13, CD23 expression was increased on both cell populations. Blood monocytes cultured for 7 days with granulocyte-macrophage colony-stimulating factor (GM-CSF) or M-CSF responded to IL-13 in a manner similar to that detected for synovial fluid-derived cells, with suppression of LPS-induced IL-1 beta, but not TNF-alpha, production. In all experiments, the responses to IL-13 were very similar to those detected to IL-4, but differed from those measured with IL-10. Thus, the responses to IL-13 by synovial fluid cells and cultured monocytes are not equal to those of blood monocytes. The similar responses to IL-4 and IL-13 support claims of a common element for signalling from the IL-4 and IL-13 receptors. Furthermore, the activity of a common receptor chain may be altered by monocyte activation and differentiation.
authors.affiliation: Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University of South Australia, Adelaide.
authors.forename: P H
authors.initials: PH
authors.lastname: Hart
authors.forename: M J
authors.initials: MJ
authors.lastname: Ahern
authors.forename: M D
authors.initials: MD
authors.lastname: Smith
authors.forename: J J
authors.initials: JJ
authors.lastname: Finlay-Jones
mesh_terms: D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis / Q000276:immunology; D001168:Arthritis / Q000276:immunology*; D015535:Arthritis, Psoriatic / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D018793:Interleukin-13 / Q000502:physiology*; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D017455:Receptors, IgE / Q000096:biosynthesis / Q000276:immunology; D013167:Spondylitis, Ankylosing / Q000276:immunology; D013582:Synovial Fluid / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D007375:Interleukin-1; D018793:Interleukin-13; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha