Exacerbation of acute inflammatory arthritis by the colony-stimulating factors CSF-1 and granulocyte macrophage (GM)-CSF: evidence of macrophage infiltration and local proliferation

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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-1β 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-1β. 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.