ARTHRITIS & RHEUMATISM Vol. 42, No. 9, September 1999, pp 1861–1869 © 1999, American College of Rheumatology SERUM LEVELS OF HYALURONAN, ANTIGENIC KERATAN SULFATE, MATRIX METALLOPROTEINASE 3, AND TISSUE INHIBITOR OF METALLOPROTEINASES 1 CHANGE PREDICTABLY IN RHEUMATOID ARTHRITIS PATIENTS WHO HAVE BEGUN ACTIVITY AFTER A NIGHT OF BED REST DANIEL-HENRI MANICOURT, PASCAL POILVACHE, ADRIEN NZEUSSEU, ANNE VAN EGEREN, JEAN-PIERRE DEVOGELAER, MARY ELLEN LENZ, and EUGENE J.-M. A. THONAR Objective. To evaluate whether and how moderate physical activity following a night of rest influences serum levels of matrix metalloproteinase 3 (MMP-3), tissue inhibitor of metalloproteinases 1 (TIMP-1), anti- genic keratan sulfate (Ag KS), and hyaluronan (HA) in 10 normal subjects and 38 patients with rheumatoid arthritis (RA). Methods. Blood was obtained from 20 RA patients before they arose from a night’s sleep, and again 1 and 4 hours after they had begun to perform moderate physical activity. Another 18 RA patients remained in bed and blood was sampled at the same time periods. Serum levels of MMP-3, TIMP-1, Ag KS, and HA were measured by enzyme-linked immunosorbent assay. Clinical activity was evaluated by the Lansbury index. Results. Both in normal subjects and in RA patients who did not remain in bed throughout the period of blood sampling, levels of HA, Ag KS, and MMP-3 increased significantly during the first hour after the subjects arose: the increase in HA and Ag KS correlated with the Lansbury index in the RA group. Three hours later, levels of Ag KS had dropped to baseline values in both groups of subjects. Levels of HA remained significantly and moderately elevated in the RA group but not in the control group, while levels of MMP-3 did not drop significantly in either group. In contrast, levels of HA, Ag KS, and MMP-3 did not change significantly in RA patients who had remained in bed. Unlike the other markers, the levels of TIMP-1 remained unchanged at the different time periods in all 3 groups studied. Conclusion. Significant changes in serum levels of some metabolic markers occur during the first hour after one arises from a night of sleep, especially in patients with RA. Measurement of the magnitude of these changes at different times in individual patients provides very different information about metabolic changes occurring in joint tissue than does measure- ment of the level of the markers at a single time point, as is usually currently reported. Matrix metalloproteinases (MMPs) play key roles in mediating the degradation of connective tissues such as articular cartilage in joints (1,2). The rate of MMP- mediated degradation is dependent upon the rates of (a) production and (b) subsequent activation of pro-MMP molecules, as well as upon the concentrations of endog- enous inhibitors, termed tissue inhibitors of metallopro- teinases (TIMPs) (3). The MMP family includes strome- lysin 1 or MMP-3, an enzyme that has broad substrate specificity and therefore is capable of degrading many components of the matrix of connective tissues, includ- ing collagen and proteoglycans (2,3). Measurement of Supported by the Fonds de De ´veloppement Scientifique of the Universite ´ Catholique de Louvain, grant 3.4597.98 from the Belgian Fund for Medical Scientific Research, the Federal Services of Scientific, Technical and Cultural Affairs of Belgium, and grants AR-39239 and AG-04736 from the NIH. Daniel-Henri Manicourt, MD: Christian de Duve Institute of Cellular Pathology, and Saint-Luc University Hospital, Universite ´ Catholique de Louvain, Brussels, Belgium; Pascal Poilvache, MD, Adrien Nzeusseu, MD, Jean-Pierre Devogelaer, MD: Saint-Luc Uni- versity Hospital, Universite ´ Catholique de Louvain, Brussels, Belgium; Anne van Egeren, BS: Universite ´ Catholique de Louvain and Christian de Duve Institute of Cellular Pathology, Brussels, Belgium; Mary Ellen Lenz, BS, Eugene J.-M. A. Thonar, PhD: Rush Medical College at Rush–Presbyterian–St. Luke’s Medical Center, Chicago, Illinois. Drs. Manicourt and Poilvache contributed equally to this work. Address reprint requests to Daniel-Henri Manicourt, MD, Department of Rheumatology, Universite ´ Catholique de Louvain 5390, Avenue Mounier, 1200 Brussels, Belgium. Submitted for publication August 26, 1998; accepted in revised form April 27, 1999. 1861