SERUM AMYLOID-A IS A SENSITIVE MARKER OF REDUCED ACTIVITY IN ARTHRITIC HAMSTERS

Acute phase protein concentrations have been advocated as objective bi ochemical measures of disease activity in rheumatoid arthritis. Howeve r the relationship of changes in acute phase proteins to the biochemic al, histologic and physiologic alterations of arthritic disease is not precisely defined. Therefore, changes in such concentrations were exa mined in association with changes in parameters of arthritis in an acu te experimental model characterized by synovial inflammation and carti lage loss. The arthritis was induced by intraarticular injection of Sy rian hamsters with lipopolysaccharide (LPS). Five acute phase proteins were monitored: murinoglobulin, inter-alpha-trypsin inhibitor, alpha( 2)-macroglobulin, alpha(1)-antiprotease, and serum amyloid A (apoSAA). Normal hamsters ran about 11 km/day; however after the onset of arthr itis, the distance fell to circa 2 km/day and then slowly rose to norm al levels over the next four days. An 8 fold elevation in apoSAA occur red with the onset of arthritis, and the levels returned towards norma l as running activity was restored. Changes in the other acute phase r eactants were less than 1.6 fold. At the time of restoration of runnin g activity, there was still substantial soft tissue swelling and cell infiltration, and joint articular cartilage remained depleted of prote oglycan. SAA mRNA was elevated in the liver suggesting systemic releas e of apoSAA-inducing cytokines from the inflamed joint. Intraperitonea l injection of LPS resulted in decreased punning, bur was much less ef fective than intraarticular LPS in inhibiting running and in elevating SAA mRNA and protein. These results in the hamster suggest that measu rements of plasma apoSAA elevation are a useful measure of current dis ease activity because they correlate with reduction in activity.