The British Journal of Rheumatology, Vol 37, 314-323, Copyright © 1998 by British Society for Rheumatology
BA 't Hart, RA Bank, JA De Roos, H Brok, M Jonker, HM Theuns, J Hakimi and JM Te Koppele
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
cross-link 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.
ORIGINAL PAPERS
Collagen-induced arthritis in rhesus monkeys: evaluation of markers for inflammation and joint degradation
Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
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