{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:17:04Z","timestamp":1791087424019,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[1994,3,1]],"date-time":"1994-03-01T00:00:00Z","timestamp":762480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Knee surg. sports traumatol. arthrosc."],"published-print":{"date-parts":[[1994,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Approximately 44% of patients develop osteoarthritis (OA) following rupture of the anterior cruciate ligament (ACL) if the injury is left unrepaired. Restoring knee stability through reconstruction, while providing symptomatic relief, has not been shown to reduce the incidence of degenerative changes. In fact, recent studies have shown that 50%\u201360% of ACL\u2010reconstructed patients go on to develop degenerative changes or frank osteo\u2010arthritis. In light of these data, our group suggests that the cause of post\u2010traumatic osteoarthritis is not biomechanical but biochemical. To test this hypothesis, we measured levels of nine cytokines which are important in modulating physiological and pathophysiological metabolism of cartilage in knee joint synovial fluid following ACL rupture. Our patient population contained both acute und chronic ACL ruptures. A total of 84 samples were collected and analyzed by enzyme\u2010linked immunosorbent assay. On the basis of the data collected, we were able to identify subgroups of patients who, on the basis of their synovial fluid cytokine profile, may be at greater or leasser risk of developing post\u2010traumatic OA. In general, patients displayed concentrations of interleukin\u20101\u03b1 (IL\u20101\u03b1), basic fibroblastic growth factor (bFGF), transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2), granulocyte\/macrophage\u2010colony stimulating factor (GM\u2010CSF), IL\u20106, and IL\u20108 that we interpreted as being consistent with an inflammatory reaction. Of great interest is the fact that the levels of these cytokines were very similar in patients 4 weeks after injury and in chronic patients, leading us to hypothesize that a chronic smoldering inflammatory reaction persists after resolution of the acute effusion. This chronic inflammatory reaction could be the cause of cartilage degeneration seen in patients after ACL reconstruction. Furthermore, this study identified two distinct subpopulations of patients with dramatically differing levels of IL\u20101\u03b2 and TNF\u2010\u03b1 in their synovial fluids. IL\u20101\u03b2 and TNF\u2010\u03b1 were either high acutely and decreased to moderate levels over time, or they were zero acutely and remained zero or low. This is likely to be a very important observation as these two cytokines are key components of the inflammatory response and are the main intra\u2010articular cytokines that provoke cartilage loss. It is our hypothesis that the group with high levels of IL\u20101\u03b2 and TNF\u2010\u03b1 contains the 50%\u201360% of the patient population which goes on to develop OA, despite knee stabilization with ACL reconstruction. Conversely, we suggest that the group whose synovial fluid contains no IL\u20101\u03b2 or TNF\u2010\u03b1 is protected from developing OA post\u2010traumatically. IL\u20101\u2010receptor antagonist protein (IRAP), the cytokine that antagonizes the biological effects of IL\u20101, was present acutely in our patient population; however, it was undetectable in chronic ACL\u2010deficient knees. These data suggest the loss with time of an important cartilage\u2010protective cytokine. The lack of IRAP chronically may allow IL\u20101\u03b2 to act in an unrestrained manner resulting in cartilage loss. In addition, IL\u20101\u03b2 promotes the secretion of many other inflammatory cytokines which may result in the chronic smoldering inflammatory reaction referred to above. These data encourage further study of the evaluation of cytokine concentrations in the ACL\u2010deficient joint as a means of obtaining both prognostic and mechanistic information of clinical value to the physician.<\/jats:p>","DOI":"10.1007\/bf01552652","type":"journal-article","created":{"date-parts":[[2005,4,20]],"date-time":"2005-04-20T15:19:13Z","timestamp":1114010353000},"page":"38-44","source":"Crossref","is-referenced-by-count":121,"title":["Synovial fluid cytokine concentrations as possible prognostic indicators in the ACL\u2010deficient knee"],"prefix":"10.1002","volume":"2","author":[{"given":"M. L.","family":"Cameron","sequence":"first","affiliation":[{"name":"<!--<label>1<\/label>--> University of Pittsburgh Medical Center Musculoskeletal Institute Ferguson Laboratory 986 Scaife Hall Pittsburgh PA 15261 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. H.","family":"Fu","sequence":"additional","affiliation":[{"name":"<!--<label>1<\/label>--> University of Pittsburgh Medical Center Musculoskeletal Institute Ferguson Laboratory 986 Scaife Hall Pittsburgh PA 15261 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. H.","family":"Paessler","sequence":"additional","affiliation":[{"name":"<!--<label>2<\/label>--> Atos\u2010Klinik Bismarckstrasse 9\u201015 D\u201069115 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Schneider","sequence":"additional","affiliation":[{"name":"<!--<label>3<\/label>--> Sportklinik Stuttgart Taubenheimstrasse 8 D\u201070372 Stuttgart Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. H.","family":"Evans","sequence":"additional","affiliation":[{"name":"<!--<label>1<\/label>--> University of Pittsburgh Medical Center Musculoskeletal Institute Ferguson Laboratory 986 Scaife Hall Pittsburgh PA 15261 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[1994,3]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4889(89)90085-2"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(89)91974-8"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.147.5.1530"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/anr.1780320310"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4889(92)90192-E"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(90)81404-C"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780330412"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/344633a0"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(88)81024-6"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112350"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/343341a0"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-0348-7405-2_19"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00186881"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113921"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1177\/036354658601400305"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100060204"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-198301000-00005"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V74.1.1.1"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2648569"},{"key":"e_1_2_1_21_2","first-page":"234","article-title":"Biology 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