Protection from collagen-induced arthritis in granulocyte-macrophage colony-stimulating factor-deficient mice

IK Campbell, MJ Rich, RJ Bischof, AR Dunn… - The Journal of …, 1998 - journals.aai.org
IK Campbell, MJ Rich, RJ Bischof, AR Dunn, D Grail, JA Hamilton
The Journal of Immunology, 1998journals.aai.org
The involvement of granulocyte-macrophage CSF (GM-CSF) in collagen-induced arthritis
(CIA) was examined using GM-CSF-deficient mice. Although CIA is generally considered to
be restricted to mice of the H-2 q or H-2 r haplotypes, we examined the role of GM-CSF in
the CIA model using GM-CSF-deficient (−/−) and wild-type (+/+) mice on a C57BL/6 (H-2 b)
background. Mice were immunized by intradermal injection at the base of the tail with chick
type II collagen followed by a repeat injection 21 days later. We found, based on both clinical …
Abstract
The involvement of granulocyte-macrophage CSF (GM-CSF) in collagen-induced arthritis (CIA) was examined using GM-CSF-deficient mice. Although CIA is generally considered to be restricted to mice of the H-2 q or H-2 r haplotypes, we examined the role of GM-CSF in the CIA model using GM-CSF-deficient (−/−) and wild-type (+/+) mice on a C57BL/6 (H-2 b) background. Mice were immunized by intradermal injection at the base of the tail with chick type II collagen followed by a repeat injection 21 days later. We found, based on both clinical and histologic assessments, 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−/− groups, suggesting a gene dosage effect. GM-CSF+/+ and GM-CSF+/− mice exhibited CIA responses ranging from mild (single digits) to severe swelling of all four paws, while in the few GM-CSF−/− mice that developed CIA the disease was confined to single digits. Despite the putative role of GM-CSF in dendritic cell development, GM-CSF-deficient mice exhibited both humoral and cellular (delayed-type hypersensitivity) responses to type II collagen; however, the cellular response was significantly reduced in the GM-CSF-deficient mice compared with the wild-type controls. These findings suggest that GM-CSF is required for CIA development in mice and support the idea that GM-CSF is a key cytokine in inflammatory joint disease.
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