Collagen-induced arthritis in rhesus monkeys: evaluation of markers for inflammation and joint degradation

The objective of this study was to analyse parameters in rhesus monkeycollagen-induced arthritis (CIA) with which the inflammation anddestruction of the joints can be described in quantitative terms. CIA wasinduced in genetically susceptible and resistant monkeys, which can bedistinguished on the basis of the dominant resistance marker Mamu- A26. Thedisease course was monitored daily using a semiquantitative scoring system.Plasma samples were collected once or twice weekly and analysed forC-reactive protein (CRP). Urines were collected overnight once a week andanalysed for excretion rates of the collagen cross- linkshydroxylysylpyridinoline (HP) and lysylpyridinoline (LP). The results showthat periods of active CIA are characterized by substantial weight loss andincreased plasma CRP levels, followed shortly thereafter by increasedexcretion rates of the collagen cross- links HP and LP. Remission of thedisease can be recognized by a decline in plasma CRP levels and especiallyan increase in body weight. The highest CRP levels were found in the mostseverely arthritic monkeys, indicating a possible relationship of theabsolute plasma CRP levels to the severity of inflammation. During periodsof active arthritis, increased excretion rates of collagen cross-links HPand LP in the urine were found. In particular, the major collagencross-link in articular cartilage, HP, showed a strong increase (9- to15-fold). The excretion rates of LP, which is considered as a bone-specificdegradation marker, only increased 4- to 6-fold, thus indicatingpredominant destruction of cartilage and less of bone. In conclusion, theseverity of CIA can be monitored in a quantitative manner using plasma CRPlevels, urinary excretion rates of HP and LP, and body weights,superimposed on semiquantitative clinical scores. The parameters alsofacilitate a more objective assessment of the effect of anti-arthriticdrugs in the model than with the clinical scores alone.