title: Comparison of the suppressive effects of interleukin-10 and interleukin-4 on synovial fluid macrophages and blood monocytes from patients with inflammatory arthritis.
abstract: This study determined the potential capacity of interleukin-10 (IL-10), compared with IL-4, to control the production of tumour necrosis factor-alpha (TNF-alpha), IL-1 beta and IL-1 receptor antagonist (IL-1ra) and the expression of major histocompatibility complex (MHC) class II antigens by monocytes/macrophages isolated from synovial fluid of patients with rheumatoid or other forms of chronic inflammatory arthritis. Mononuclear cells were isolated from synovial fluid and peripheral blood and incubated with or without lipopolysaccharide (LPS), and with or without IL-10 (100 U/ml, 10 ng/ml) or IL-4 (10 ng/ml) for 22 hr. TNF-alpha, IL-1 beta and IL-1ra levels were measured by enzyme-linked immunosorbent assay (ELISA) in the culture supernatants, and MHC class II expression was examined on the monocytes/macrophages by flow cytometry. IL-10, unlike IL-4, decreased TNF-alpha production by LPS-stimulated synovial fluid cells to the same extent as by LPS-stimulated peripheral blood cells from the same patients. IL-10 and IL-4 suppressed equally IL-1 beta production by the same cells. However, only IL-4 significantly increased IL-1ra production by synovial fluid mononuclear cells. Synovial fluid cells expressed increased levels of MHC class II antigen, and these levels were not as efficiently suppressed by IL-10 as they were for peripheral blood cells. Because IL-10 and IL-4 differentially regulate TNF-alpha and IL-1ra production by synovial fluid mononuclear cells, selective use of either IL-10 or IL-4 in the treatment of chronic inflammatory conditions will depend on whether TNF-alpha or IL-1, respectively, is established as primarily responsible for the maintenance of the chronic inflammatory condition.
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: D001168:Arthritis / Q000276:immunology*; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007108:Immune Tolerance; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012795:Sialoglycoproteins / Q000096:biosynthesis; D013582:Synovial Fluid / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4