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 art hritis. 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 admi nistration of CSF-1 or GM-CSF following mBSA administration into the knee r esulted in the exacerbation of arthritis. This included synovial hyperplasi a and joint inflammation, most evident at 7 and 14 days post-mBSA administr ation, 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 2 1 days post-mBSA administration, similar to the effects of IL-1 beta in thi s model, reported here and previously. Macrophages expressing Mac-2 and F4/ 80 were a prominent feature of the pathology observed, particularly the inf iltration of Mac-2(+) macrophages seen in all mice administered CSF-1, GM-C SF or IL-1 beta. Present in inflamed knees was a locally dividing populatio n of cells which included Mac-2(+) and F4/80(+) macrophages. These studies demonstrate that CSF-1 and GM-CSF can exacerbate and prolong the histopatho logy of acute inflammatory arthritis and lend support to monocytes/macropha ges being a driving influence in the pathogenesis of inflammatory arthritis .