PROTECTION FROM COLLAGEN-INDUCED ARTHRITIS IN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR-DEFICIENT MICE

The involvement of granulocyte-macrophage CSP (GM-CSF) in collagen-ind uced arthritis (CIA) was examined using GM-CSF-deficient mice. Althoug h CIA is generally considered to be restricted to mice of the H-2(q) o r H-2(r) haplotypes, we examined the role of GM-CSF in the CIA model u sing GM-CSF-deficient (-/-) and wild-type (+/+) mice on a C57BL/6 (H-2 (b)) background. Mice were immunized by intradermal injection at the b ase of the tail with chick;type II collagen followed by a repeat injec tion 21 days later. We found, based on both clinical and histologic as sessments, that wild-type mice on this background developed severe CIA , while the GM-CSF-deficient mice had virtually no disease. Mice that were heterozygous for the GM-CSF gene (+/-) collectively displayed an intermediate response between those of the GM-CSF+/+ and GM-CSF-/- gro ups, suggesting a gene dosage effect, GM-CSF+/+ and GM-CSF+/- mice exh ibited CIA responses ranging from mild (single digits) to severe swell ing of ail four paws, while in the few GM-CSF-/- mice that developed C IA the disease was confined to single digits. Despite the putative rol e of GM-CSF in dendritic cell development, GM-CSF-deficient mice exhib ited both humoral and cellular (delayed-type hypersensitivity) respons es to type II collagen; however, the cellular response was significant ly reduced in the GM-CSF-deficient mice compared with the wild-type co ntrols. These findings suggest that GM-CSF is required for CIA develop ment in mice and support the idea that GM-CSF is a key cytokine in inf lammatory joint disease.