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

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.