Serum amyloid A is a sensitive marker of reduced activity in arthritic hamsters

Abstract

Acute phase protein concentrations have been advocated as objective biochemical measures of disease activity in rheumatoid arthritis. However, the relationship of changes in acute phase proteins to the biochemical, histologic and physiologic alterations of arthritic disease is not precisely defined. Therefore, changes in such concentrations were examined in association with changes in parameters of arthritis in an acute experimental model characterized by synovial inflammation and cartilage loss. The arthritis was induced by intraarticular injection of Syrian hamsters with lipopolysaccharide (LPS). Five acute phase proteins were monitored: murinoglobulin, inter-α-trypsin inhibitor, α₂-macroglobulin, α₁-antiprotease, and serum amyloid A (apoSAA). Normal hamsters ran about 11 km/day; however, after the onset of arthritis, the distance fell to circa 2 km/day and then slowly rose to normal levels over the next four days. An 8 fold elevation in apoSAA occurred with the onset of arthritis, and the levels returned towards normal as running activity was restored. Changes in the other acute phase reactants were less than 1.6 fold. At the time of restoration of running activity, there was still substantial soft tissue swelling and cell infiltration, and joint articular cartilage remained depleted of proteoglycan. SAA mRNA was elevated in the liver suggesting systemic release of apoSAA-inducing cytokines from the inflamed joint. Intraperitoneal injection of LPS resulted in decreased running, but was much less effective than intraarticular LPS in inhibiting running and in elevating SAA mRNA and protein. These results in the hamster suggest that measurements of plasma apoSAA elevation are a useful measure of current disease activity because they correlate with reduction in activity.