Interferon-gamma inhibits interleukin-1beta-induced matrix metalloproteinase production by synovial fibroblasts and protects articular cartilage in early arthritis.

Arthritis Res Ther. 2010;12(2):R49
Authors: Page CE, Smale S, Carty SM, Amos N, Lauder SN, Goodfellow RM, Richards PJ, Jones SA, Topley N, Williams AS
INTRODUCTION: The first few months after symptom onset represents a pathologically distinct phase in rheumatoid arthritis (RA). We used relevant experimental models to define the pathological role of interferon-gamma (IFN-gamma) during early inflammatory arthritis. METHODS: We studied IFN-gamma’s capacity to modulate interleukin-1beta (IL-1beta) induced degenerative responses using RA fibroblast-like synoviocytes (FLS), a bovine articular cartilage explant (BACE)/RA-FLS co-culture model and an experimental inflammatory arthritis model (murine antigen-induced arthritis (AIA)). RESULTS: IFN-gamma modulated IL-1beta driven matrix metalloproteinases (MMP) synthesis resulting in the down-regulation of MMP-1 and MMP-3 production in vitro. IFN-gamma did not affect IL-1beta induced tissue inhibitor of metalloproteinase-1 (TIMP-1) production by RA FLS but skewed the MMP/TIMP-1 balance sufficiently to attenuate glycosaminoglycan-depletion in our BACE model. IFN-gamma reduced IL-1beta expression in the arthritic joint and prevented cartilage degeneration on Day 3 of AIA. CONCLUSIONS: Early therapeutic intervention with IFN-gamma may be critical to orchestrate tissue-protective responses during inflammatory arthritis.
PMID: 20307272 [PubMed – indexed for MEDLINE]