Protection from collagen-induced arthritis in granulocyte-macrophage colony-stimulating factor-deficient mice
Details
Publication Year 1998-10-01, Volume 161, Issue #7, Page 3639-3644
Journal Title
JOURNAL OF IMMUNOLOGY
Publication Type
Journal Article
Abstract
The involvement of granulocyte-macrophage CSP (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 ail 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.
Publisher
AMER ASSOC IMMUNOLOGISTS
Keywords
CHRONIC INFLAMMATORY ARTHRITIS; TUMOR-NECROSIS-FACTOR; RHEUMATOID-ARTHRITIS; IFN-GAMMA; GM-CSF; DENDRITIC CELLS; HUMAN-MONOCYTES; FACTOR AUGMENTS; SUSCEPTIBILITY; NEUTROPHILS
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Creation Date: 1998-10-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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