title: Exacerbation of acute inflammatory arthritis by the colony-stimulating factors CSF-1 and granulocyte macrophage (GM)-CSF: evidence of macrophage infiltration and local proliferation.
abstract: CSF-1 and GM-CSF have been implicated in the pathogenesis of rheumatoid arthritis. We report the effects of CSF-1 and GM-CSF in the development of an acute methylated bovine serum albumin (mBSA)-induced murine arthritis model. Examination of histopathological features revealed that the systemic administration of CSF-1 or GM-CSF following mBSA administration into the knee resulted in the exacerbation of arthritis. This included synovial hyperplasia and joint inflammation, most evident at 7 and 14 days post-mBSA administration, and the appearance of erosive pannus tissue. The exacerbation by CSF-1 and GM-CSF was not sustained but declined in incidence and severity by 21 days post-mBSA administration, similar to the effects of IL-1beta in this model, reported here and previously. Macrophages expressing Mac-2 and F4/80 were a prominent feature of the pathology observed, particularly the infiltration of Mac-2+ macrophages seen in all mice administered CSF-1, GM-CSF or IL-1beta. Present in inflamed knees was a locally dividing population of cells which included Mac-2+ and F4/80+ macrophages. These studies demonstrate that CSF-1 and GM-CSF can exacerbate and prolong the histopathology of acute inflammatory arthritis and lend support to monocytes/macrophages being a driving influence in the pathogenesis of inflammatory arthritis.
authors.affiliation: Inflammation Research Centre, The University of Melbourne, Department of Medicine at The Royal Melbourne Hospital, Parkville, Victoria, Australia. r.bischof@vet.unimelb.edu.au
authors.forename: R J
authors.initials: RJ
authors.lastname: Bischof
authors.forename: D
authors.initials: D
authors.lastname: Zafiropoulos
authors.forename: J A
authors.initials: JA
authors.lastname: Hamilton
authors.forename: I K
authors.initials: IK
authors.lastname: Campbell
mesh_terms: D000208:Acute Disease; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology; D002455:Cell Division / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000633:toxicity*; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology / Q000633:toxicity; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000633:toxicity*; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D007375:Interleukin-1; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor