Studies indicate that the cytokines granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-17 have important pathogenic roles in rheumatoid arthritis (RA). In vivo experiments have shown that blockade of either cytokine has beneficial effects on disease severity. Plater-Zyberk and colleagues, therefore, studied the effects of GM-CSF and IL-17 double blockade in a mouse model of RA-like disease.
Streptococcal cell wall arthritis was induced in one knee of IL-17 receptor (IL-17R)-knockout C57Bl/6 mice and wild-type mice. The mice were then treated with antibodies against GM-CSF, IL-1β or tumor necrosis factor (TNF) by intraperitoneal injection.
Mice treated with GM-CSF blockade had significantly decreased joint swelling in their diseased knee; this effect persisted until 4 days after the final injection. TNF blockade with etanercept had no effect on joint swelling, whereas IL-1β blockade caused a modest decrease in swelling. Mice treated with GM-CSF or IL-1β blockade had significantly reduced knee cartilage damage. The beneficial effects of GM-CSF blockade on joint swelling and cartilage damage were significantly greater in IL-17R knockout mice than in wild-type mice.
The authors conclude that these results support the hypothesis that blockade of GM-CSF or IL-17 has potential therapeutic benefit in an RA-like arthritis model. Inhibition of both GM-CSF and IL-17 might be especially effective in patients with RA who do not respond to anti-TNF therapy.
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GM-CSF and IL-17 blockade shows beneficial effects in a mouse model of arthritis. Nat Rev Rheumatol 4, 446 (2008). https://doi.org/10.1038/ncprheum0868
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DOI: https://doi.org/10.1038/ncprheum0868