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

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Author: Hart, B.A. 't · Bank, R.A. · Roos, J.A.D.M. de · Brok, H. · Jonker, M. · Theuns, H.M. · Hakimi, J. · Koppele, J.M.Te.
Institution: Centraal Instituut voor Voedingsonderzoek TNO
Source:British Journal of Rheumatology, 3, 37, 314-323
Identifier: 234588
Keywords: Nutrition · Collagen-induced arthritis · Disease markers · Rhesus monkey · C reactive protein · Collagen · Cyclosporin a · Deoxypyridinoline · Pyridinoline · Animal experiment · Animal model · Arthritis · Blood level · Cartilage degeneration · Controlled study · Diagnostic value · Disease activity · Disease course · Disease marker · Disease predisposition · Disease severity · Female · Inflammation · Joint degeneration · Male · Nonhuman · Priority journal · Remission · Rhesus monkey · Urine level · Weight gain · Weight reduction · Amino Acids · Animals · Antirheumatic Agents · Arthritis, Experimental · Biological Markers · C-Reactive Protein · Collagen · Cross-Linking Reagents · Cyclosporine · Female · Joints · Macaca mulatta · Male · Synovial Fluid · Weight Loss


The objective of this study was to analyse parameters in rhesus monkey collagen-induced arthritis (CIA) with which the inflammation and destruction of the joints can be described in quantitative terms. CIA was induced in genetically susceptible and resistant monkeys, which can be distinguished on the basis of the dominant resistance marker Mamu-A26. The disease course was monitored daily using a semiquantitative scoring system. Plasma samples were collected once or twice weekly and analysed for C-reactive protein (CRP). Urines were collected overnight once a week and analysed for excretion rates of the collagen cross-links hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP). The results show that periods of active CIA are characterized by substantial weight loss and increased plasma CRP levels, followed shortly thereafter by increased excretion rates of the collagen cross-links HP and LP. Remission of the disease can be recognized by a decline in plasma CRP levels and especially an increase in body weight. The highest CRP levels were found in the most severely arthritic monkeys, indicating a possible relationship of the absolute plasma CRP levels to the severity of inflammation. During periods of active arthritis, increased excretion rates of collagen cross-links HP and LP in the urine were found. In particular, the major collagen crosslink in articular cartilage, HP, showed a strong increase (9- to 15-fold). The excretion rates of LP, which is considered as a bone-specific degradation marker, only increased 4- to 6-fold, thus indicating predominant destruction of cartilage and less of bone. In conclusion, the severity of CIA can be monitored in a quantitative manner using plasma CRP levels, urinary excretion rates of HP and LP, and body weights, superimposed on semiquantitative clinical scores. The parameters also facilitate a more objective assessment of the effect of anti-arthritic drugs in the model than with the clinical scores alone.