Increased serum levels of non-collagenous matrix proteins (cartilage oligomeric matrix protein and melanoma inhibitory activity) in marathon runners.
OBJECTIVE
Marathon runners have an increased risk of developing joint disease. During and after a 42-km run, elevation of multiple cytokines occurs in the blood, reflecting inflammatory processes. We compared this cytokine response with serum levels of cartilage oligomeric matrix protein (COMP) and melanoma inhibitory activity (MIA), two markers for joint metabolism and/or damage.


METHODS
Serum from eight endurance-trained runners was collected shortly before the start of a marathon run, after 31 km, 42 km, 2 h after the end, on the first and on the second morning after the run. For comparison, serum was obtained from 35 healthy controls and 80 patients with knee joint injury, rheumatoid arthritis or osteoarthritis. Serum levels of C-reactive protein (CRP), interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1RA), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble interleukin-6 receptor (sIL-6R, gp80), soluble tumor necrosis factor receptor II (sTNFRII, p75), COMP and MIA were measured by ELISA.


RESULTS
Compared with healthy controls, the runner's baseline serum levels of TNF-alpha, sIL-6R, COMP and MIA were significantly increased. COMP and MIA levels, higher than the upper normal limits of 5 microg/ml and 6 ng/ml respectively, were found in seven and five of eight runners. The elevated levels of COMP were similar to those found in joint injury or osteoarthritis, and the elevated levels of MIA were comparable to those reported in rheumatoid arthritis. During the run, the serum levels of IL-1RA, IL-6, TNF-alpha and COMP rose significantly, and gradually returned to baseline within 24 h. Only modest changes of CRP, sIL-6R, sTNFRII and MIA occurred during the run. Late elevations of CRP and MIA were observed after 24 and 48 h. The correlation analysis suggests associations between COMP, sIL-6R, TNF-alpha, IL-1RA on one hand and sTNFRII, and MIA and CRP on the other hand.


CONCLUSIONS
Elevated baseline levels of COMP and MIA might reflect increased joint matrix turnover and/or damage due to prior extreme physical training. During the run, COMP was increasing possibly due to the severe physical strain on joint structures, associated with the early inflammation. After the run, MIA and CRP increased within 24 h, suggesting a correlation with later inflammatory processes. Thus, our data suggest that COMP and MIA are markers for distinct aspects of joint metabolism and/or damage in both disease and sport.
Neidhart
M
M
Center for Experimental Rheumatology, University Hospital, Zürich, Switzerland. michel-neidhart@ruz.usz.ch
Müller-Ladner
U
U
Frey
W
W
Bosserhoff
A K
AK
Colombani
P C
PC
Frey-Rindova
P
P
Hummel
K M
KM
Gay
R E
RE
Häuselmann
H
H
Gay
S
S
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000097:blood*; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007718:Knee Injuries / Q000097:blood; D009363:Neoplasm Proteins / Q000097:blood*; D010003:Osteoarthritis / Q000097:blood; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000097:blood; D019947:Receptors, Interleukin-6 / Q000097:blood; D012420:Running / Q000502:physiology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016326:Extracellular Matrix Proteins; D007375:Interleukin-1; D015850:Interleukin-6; C090059:MIA protein, human; D009363:Neoplasm Proteins; D017472:Receptors, Interleukin-1; D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein