Expression of rabbit C-reactive protein in transgenic mice inhibits development of antigen-induced arthritis

Objective: Greactive protein (CkP) Is a plasma protein of hepatic origin thought to play an important role in host defences. We used transgenic mice, Capable of expressing high levels of rabbit CRP (serum concentration > 50 mu g/mL) in response to dietary manipulation, to determine whether high levels of this acute-phase reactant can alter the course of experimentally induced moncarticular arthritis. Method: Arthritis was induced by a single injection of methylated bovine serum albumin (mBSA) on day 0 followed by injections of interleukin (IL)-1 beta. Results: In transgenic animals in which CRP expression had been suppressed (serum concentration < 10 mu g/mL), inflammatory arthritis began to develop by day 4 and was fully developed by 7 days after the mBSA challenge. This arthritis was characterized by marked inflammatory cell infiltrates in soft tissues, synovitis, pannus, cartilage loss, and bone erosion. By contrast, when CRP expression was induced, resulting in serum concentrations > 50 mu g/mL on the day of mBSA and IL-1 beta injections, the inflammatory response was dramatically reduced at day 7. These mice manifested little to no evidence of joint inflammation. This antiinflammatory effect of CRP was seen in animals with high CRP levels on days 0-1 following immunization and did not require elevated CRP levels during the period of rapid inflammatory progression, 4-7 days after challenge. Conclusion: CRP, expressed at the time of antigenic stimulation, effectively blocked the subsequent development of inflammatory arthritis in this model by altering the immune or inflammatory responses.