The colony-stimulating factors and collagen-induced arthritis: exacerbation of disease by M-CSF and G-CSF and requirement for endogenous M-CSF

There is increasing evidence that the colony-stimulating factors (CSFs) may play a part in chronic inflammatory autoimmune diseases, such as rheumatoi d arthritis (RA). We examined the involvement of macrophage CSF (M-CSF or C SF-1) and granulocyte CSF (G-CSF) in collagen-induced arthritis (CIA), a mu rine model of EW, Daily injections of M-CSF or G-CSF, 20-24 days postprimar y immunization with type II collagen, exacerbated disease symptoms in subop timally immunized DBA/1 mice. Support for the involvement of endogenous M-C SF in CIA was obtained by studies in which neutralizing monoclonal antibody reduced the severity of established CIA and also by studies showing the re sistance of M-CSF-deficient op/op mice to CIA induction, These studies show that M-CSF and G-CSF can be proinflammatory in CIA and provide evidence th at macroghage- and granulocyte-lineage tells can exacerbate CIA. Our result s also show that M-CSF-dependent cells are essential for CIA development, s uggesting M-CSF may be a suitable target for therapeutic intervention in RA .