title: IL-10 receptor dysfunction in macrophages during chronic inflammation.
abstract: The immunosuppressive activity of interleukin-10 (IL-10) makes this cytokine a potentially important clinical tool to reduce inflammatory responses in various diseases. Its efficacy as a therapeutic modality is dependent on the responsiveness of immune cells. We report that macrophages from mice chronically infected with the LP-BM5 retrovirus had a reduced capacity to respond to IL-10 in vitro. The ability of IL-10 to inhibit lipopolysaccharide-induced production of tumor necrosis factor (TNF) alpha and IL-6 was significantly reduced in both alveolar and peritoneal macrophages from infected versus uninfected mice. IL-10 hyporesponsiveness was not related to direct infection by the retrovirus, because bone marrow-derived macrophages infected in vitro with LP-BM5 were as responsive to IL-10 as were uninfected bone marrow-derived macrophages. TNF-alpha appeared to contribute to development of IL-10 hyporesponsiveness, because exposure of normal macrophages to TNF-alpha but not interferon-gamma reduced macrophage responsiveness to IL-10. Reverse transcriptase-PCR and flow cytometry demonstrated normal expression of the alpha and beta chains of the IL-10 receptor in macrophages from infected mice, suggesting that IL-10 hyporesponsiveness is not related to a change in receptor expression. The potential role of reduced IL-10 responsiveness in the chronicity of inflammation in this and other diseases is discussed.
authors.affiliation: Department of Microbiology and Immunology, University of Kentucky, College of Medicine, Lexington 40536-0084, USA.
authors.forename: R
authors.initials: R
authors.lastname: Avdiushko
authors.forename: D
authors.initials: D
authors.lastname: Hongo
authors.forename: H
authors.initials: H
authors.lastname: Lake-Bullock
authors.forename: A
authors.initials: A
authors.lastname: Kaplan
authors.forename: D
authors.initials: D
authors.lastname: Cohen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D017563:Lung Diseases, Interstitial / Q000235:genetics / Q000276:immunology / Q000821:virology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D053701:Receptors, Interleukin-10; D012192:Retroviridae Infections / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10