参麦注射液对骨关节炎模型动物关节液中白细胞介素—1水平？…

目的 探讨参麦注射液对骨关节炎模型动物关节液中白细胞介素－１（ＩＬ－１）水平的影响。方法 建立骨关节炎动物模型,随机分成３组,１参麦组,２盐盐组,３正常对照组。１、２组分别注射参麦注射液和无菌生理盐水,３组不作注射。按设计分批次处死,检测模型动物关节液中ＩＬ－１水平。结果 参麦注射能够明显降低模型动物关节液中ＩＬ－１的升高水平。结论 注射液通过抑制关节液中ＩＬ－１水平的异常升高发挥对骨关节炎的防治     

参麦注射液对骨关节炎模型动物关节液中白细胞介素～1水平的影响

目的　探讨参麦注射液对骨关节炎模型动物关节液中白细胞介素-1(IL-1)水平的影响。方法　建立骨关节炎动物模型,随机分成3组Ⅰ参麦组,Ⅱ盐水组,Ⅲ正常对照组。Ⅰ、Ⅱ组分别注射参麦注射液和无菌生理盐水,Ⅲ组不作注射。按设计分批次处死,检测模型动物关节液中IL-1水平。结果　参麦注射液能够明显降低模型动物关节液中IL-1的升高水平。结论　参麦注射液通过抑制关节液中IL-1水平的异常升高发挥对骨关节炎的防治作用。     

白细胞介素-6对人冠状动脉平滑肌细胞表达基质金属蛋白酶-3和基质金属蛋白酶抑制剂-1的影响

目的 探讨炎症因子白细胞介素-6（IL-6）对人冠状动脉（冠脉）平滑肌细胞表达基质金属蛋白酶-3（MMP-3）和基质金属蛋白酶组织抑制剂-1（TIMP-1）的影响.方法 （1）应用10 μg/L浓度的IL-6刺激人冠脉平滑肌细胞,分别在共同培养0、2、4,8、24、36小时后收集细胞.（2）应用不同浓度的IL-6（0、5、10、50 μg/L）刺激人冠脉平滑肌细胞,共同培养6小时后收集细胞.（3）应用实时荧光定量PCR方法检测MMP-3、TIMP-1基因的表达量.结果 同剂量IL-6刺激下,MMP-3的表达量在2小时时就开始发生上调,8小时达高峰,而后开始下降;在不同剂量IL-6刺激下,MMP-3的表达量在实验剂量范围内随着IL-6的剂量加大呈上升趋势.而TIMP-1表达量在2小时时就开始发生下调,4小时达最低,而后开始上升;在不同剂量IL-6刺激下,TIMP-1的表达量在实验剂量范围内随着IL-6的剂量加大呈下降趋势.结论 炎症因子IL-6对人冠脉平滑肌细胞中斑块稳定相关标记物MMP-3、TIMP-1表达的影响,可能是炎症在急性冠脉综合征（ACS）发生发展中起作用.     

骨关节炎兔血清中软骨寡聚基质蛋白和基质金属蛋白酶-3水平

目的 探讨血清软骨寡聚基质蛋白(COMP)与基质金属蛋白酶(MMP)-3检测应用于临床评估骨关节炎(OA)软骨病理改变的可能性.方法 伸直位石膏管型制动16只兔右后膝关节制作OA模型.以造模时间不同分为造模2周、造模6周,左后膝关节未造模故为对照组.X线影像学与病理观察模型关节的变化;评估关节软骨降解程度(OA积分);ELISA检测兔血清COMP、MMP-3水平;分析血清COMP、MMP-3水平与OA积分间的相关性.结果 (1)造模2周影像学变化较造模前不明显;造模6周兔胫骨平台边缘不光滑,关节间隙变窄,表面有毛刺样增生,胫骨平台及股骨内髁外侧可见唇样增生.(2)OA关节病变的形态学观察:造模2周兔关节软骨表面粗糙,表层裂隙;软骨细胞弥漫增多,排列紊乱;OA积分为(4.000±2.204)分.造模6周兔关节软骨表层可见较多裂隙延伸向下深达辐射层;裂隙周围可见脱水固缩坏死的软骨细胞且排列紊乱,部分成簇增生,各层结构不易分辨,有血管翳通过;OA积分为(10.620±1.408)分,与造模2周比,P=0.000.(3)造模2周兔血清COMP[(3.64±0.18)μg/L]、MMP-3[(1.99±0.81)μg/L]水平高于造模前[COMP(3.35±0.20)μg/L,MMP-3(1.61±0.71)μg/L];造模6周兔血清COMP[(3.96±0.44)μg/L]、MMP-3[(3.44±0.91)μg/L]水平高于造模前和造模2周,差异有统计学意义(P值均＜0.05).血清COMP、MMP-3水平与OA积分呈线性相关关系(r值均＞0.710,P值均小于0.05).结论 OA血清中COMP和MMP-3水平对评估OA软骨降解程度具有重要意义.

Abstract：

Objectiye To study the levels of cartilage oligomeric matrixprotein (COMP) and matrix metalloproteinase-3 (MMP-3) in the serum fluid of osteoarthritic rabbit models and their relationships with the severity of pathological changes, so as to investigate their correlation with osteoarthritis(OA). Methods The osteoarthritic animal models were get from immobilizing the right knees of 18 rabbits in full extension using plaster cast. Knee joint pathological changes of 2,6 weeks were examined for pathological severity of OA; ELISA sandwich method was used to measure the levels of COMP and MMP-3 in serum before and after modeling( at 2, 6 weeks respectively); X ray of model keens was also obtained in different period.Correlation analysis was performed to demonstrate the relationship between the levels of COMP, MMP-3 in the serum and the pathological severity of OA. Results ( 1 ) Morphological observations: immobilizing the right knees of rabbits in full extension using plaster cast was a reliable methed for osteoarthritic animal models and the typical histopathologic character was seen; the severity of osteoarthritisgradually increased with time extended. (2) The levels of COMP[(3.64 ±0. 18)μg/L], MMP-3 [(1.99 ±0. 81 ) μg/L]in the serum of 2 weeks osteoarthritic animal models were higher than those before immobilizing with plaster cast [COMP(3.35 ±0. 20) μg/L,MMP-3( 1.61 ±0. 71 ) μg/L]. The levels of COMP[(3.96 ±0. 44) μg/L],MMP-3[(3.44 ±0. 91) μg/L] of 6 weeks were much higher,with a significant difference(P ＜0.05). The levels of COMP, MMP-3 in serum had a linear correlation with the pathological severity of OA (r ＞0. 710,and P ＜ 0. 05 ). Conclusion The levels of COMP and MMP-3 in serum can help to predict and evaluate the progression of OA.     

白细胞介素-18在骨关节炎滑膜细胞中的表达及意义

目的 了解白细胞介素(IL)-18在骨关节炎(OA)患者和非OA患者滑膜细胞中表达的差异.方法 取OA患者(22例)与非OA患者(8例)关节滑膜组织,分别原代培养滑膜细胞,采用酶联免疫吸附测定法(ELISA)定量检测2组滑膜细胞培养上清液中IL-18蛋白的表达水平,采用免疫细胞化学方法 定性观察IL-18在2组滑膜细胞问表达的差异,统计学处理采用t检验.结果 ELISA检测OA患者细胞培养上清液中IL-18的含量为(63.9±21.4)pg/ml, 非OA患者细胞培养上清液中IL-18的含量为(17.7±1.5)pg/ml,2组比较差异有统计学意义(t=10.044,P<0.01);免疫细胞化学方法 显示在OA患者滑膜细胞中IL-18蛋白的表达呈阳性.胞质为棕黄色深染,而在非OA患者滑膜细胞中胞质淡染.结论 IL-18在OA关节滑膜细胞中表达上调, 提示IL-18可能直接参与了OA的发病过程.     

IL-1β、IL-6对人冠脉平滑肌细胞表达基质金属蛋白酶-3及基质金属蛋白酶组织抑制剂-1的影响

目的研究炎症因子白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）对人冠脉平滑肌细胞表达基质金属蛋白酶-3（MMP-3）和基质金属蛋白酶组织抑制剂-1（TIMP-1）的影响。方法①应用20μg/L的IL-1β、10μg/L的IL-6刺激人冠脉平滑肌细胞,分别在共同培养0、2、4、8、24、36h后收集细胞。②应用不同浓度的IL-1β（0、5、20、40μg/L）、IL-6（0、5、10、50μg/L）刺激人冠脉平滑肌细胞,共同培养6h后收集细胞。③应用实时荧光定量PCR的方法检测细胞内MMP-3和TIMMP-1基因的表达量。结果同剂量IL-1β、IL-6刺激下,MMP-3的表达量在2h时就开始上调,8h达高峰,而后开始下降;在不同剂量IL-1β、IL-6刺激下,MMP-3的表达量在实验剂量范围内随着IL-1β、IL-6的剂量加大呈上升趋势（IL-1β:r=0.907,P=0.000;IL-6:r=0.919,P=0.000）。而TIMP-1表达量在2h时就开始下调,IL-1β刺激下在8h左右达最低,IL-6刺激下在4h左右达最低,而后开始上升;在不同剂量IL-1β、IL-6刺激下,TIMP-1的表达量在实验剂量范围内随着IL-1β、IL-6的剂量加大呈下降趋势（IL-1β:r=-0.768,P=0.004;IL-6:r=-0.799,P=0.002）。结论炎症因子IL-1β、IL-6对冠脉平滑肌细胞中斑块稳定相关标记物MMP-3、TIMP-1表达的影响,可能是炎症在急性冠脉综合征的发生发展中起非常重要作用的机制之一。     

基质金属蛋白酶3与动脉粥样硬化关系研究的进展

本文概述了基质金属蛋白酶3与动脉粥样硬化之间的关系,并重点介绍了基质金属蛋白酶家族及其来源,基质金属蛋白酶分类、结构、调节、共同特征,以及基质金属蛋白酶-3在动脉粥样硬化中的表达及作用.     

急性脑梗死患者基质金属蛋白酶-2和白细胞介素-1β含量的变化

脑梗死后缺血/再灌注(I/R)损伤是一个复杂的缺血级联反应,涉及多种机制,基质金属蛋白酶-2(MMP-2)可通过降解基底膜,破坏血脑屏障,形成血管源性脑水肿,激活炎性细胞因子,引起炎性细胞浸润,直接导致持续性的细胞凋亡等在脑梗死后I/R损伤中发挥了重要的病理生理效应。本文从临床上动态观察MMP-2和白细胞介素-1β(IL-1β)含量变化与脑梗死的关系及其相关性,探讨二者在脑梗死发生发展中的作用。     

骨关节炎患者关节软骨和滑膜金属蛋白酶-1和-3的表达

骨关节炎 (ＯＡ)的病理特征为关节软骨的进行性变性和破坏 ,但其确切的发病机制未明。近年研究提示 ,ＯＡ的这种病理改变与金属蛋白酶 (ＭＭＰｓ)对细胞外基质的降解作用可能有关[1] 。我们检测了ＭＭＰ 1、 3在ＯＡ软骨和滑膜组织中的表达状况 ,以探讨两者在ＯＡ发病中的作用。一、对象与方法1 实验对象 :膝ＯＡ病人均符合Ａｌｔｍａｎ等[2 ] 的ＯＡ诊断标准。正常对照组包括意外受伤截肢患者或意外死亡者。膝ＯＡ患者 14例 ,男 5例 ,女 9例 ,平均年龄 (5 8 2± 11 1)岁 ;正常对照组 11例 ,男 5例 ,女 6例 ,平均年龄 (5 1 3± 9 6 )岁。2 …     

基质金属蛋白酶-13和胰岛素样生长因子-1在大骨节病关节滑膜中的表达及临床意义

目的 探讨基质金属蛋白酶(MMP-13)和胰岛素样生长因子(IGF)-l在膝关节骨关节炎(OA)和大骨节病(KBD)滑膜病变中的作用机制并比较其异同.方法 提取18例OA患者,13例KBD患者,6名健康对照者的滑膜组织及关节液,采用免疫组织化学方法检测关节滑膜组织中MMP-13和IGF-1的阳性染色区的平均吸光度(A),通过酶联免疫吸附试验(ELISA)法测定关节滑液中MMP-13和IGF-1的蛋白含量.采用单因素方差分析和LSD-t检验进行统计学分析.结果 在本组37份关节滑膜组织及关节滑液标本中:①KBD患者滑膜组织各层MMP-13阳性染色区的4值(692±131,354±10l,415±62)与OA组患者滑膜组织各层平均A(452±57,366±65,652±86)比较差异无统计学意义(P＞0.05),与健康对照组各层A值(541±98,524±202,379±94)比较差异有统计学意义(P＜0.05).②KBD患者滑膜组织各层lGF-1蛋白表达的A值(3ll±174,235±95,412±109)低于OA组(452±57,652±75,544±64)及健康对照组(25l±29,336±54,388±76),且差异有统计学意义(P＜0.05).③KBD患者关节滑液MMP-13含量(2.02±1.12)与OA组(0.93±0.51)比较差异无统计学意义(P＞0.05),但高于健康对照组(2.33±0.29),且差异有统计学意义(P＜0.05).④KBD患者关节滑液IGF-1含量(2.87±1.48)高于OA组(1.27±0.33)和健康对照组(0.93±1.07)且差异均有统计学意义(P＜0.05).结论 ①与OA一样,KBD患者关节的滑膜病变可能作为软骨退变和关节毁损的一个环节而存在;②MMP-13作为OA发病机制中软骨细胞外基质(ECM)主要的分解性因子,可能参与了OA和KBD患者滑膜病理演变过程;③IGF-1作为ECM合成性因子,也参与了OA和KBD患者的滑膜病变过程,但对两种疾病ECM的修复机制可能不同.     

Detection of stromelysin in synovial fluid and serum from patients with rheumatoid arthritis and osteoarthritis

Summary Stromelysin levels were measured using a one-step sandwich immunoassay in synovial fluid (SF) obtained from 31 patients with rheumatoid arthritis (RA) (31 samples) and 13 patients with osteoarthritis (OA) (13 samples) and in serum from 81 patients with RA (106 samples), 12 with OA (14 samples), 12 with gouty arthritis (gout) (14 samples), and 8 with osteoporosis (OP) (14 samples) to identify differences in the levels in these diseases as well as correlations with clinical parameters in RA. SF stromelysin levels were significantly higher in RA than in OA, and rose with increasing joint destruction in the former. No significant correlations were found between the SF stromelysin level in RA and various clinical parameters, except for the volume of SF which showed a correlation. Serum levels of stromelysin were highest in RA, gout, OA, and osteoporosis in decreasing order, and in RA were correlated with the Steinbrocker Stage. A significant correlation was also found between the serum stromelysin level and number of swollen joints, and correlations with the Lansbury index, ESR, CRP, WBC and Plt. The stromelysin level in SF was thought to be a useful parameter of local joint involvement and that in serum of the severity of systemic joint inflammation.     

Morphological features of articular cartilage and synovial membrane in osteoarthritis and rheumatoid arthritis

Osteoarthritis (OA) and rheumatoid arthritis (RA) do not show any specific morphological findings. However, there are many morphological findings which are common to each disease. In the current study, we describe morphological changes of articular cartilage and synovial membrane during progression of joint destruction in OA and RA, respectively.     

骨关节炎患者软骨及滑膜高迁移率族蛋白1的表达

目的探讨高迁移率族蛋白1(HMGB1)与骨关节炎(OA)发生和发展的关系。方法采用免疫组织化学方法观察42例老年 OA 患者关节软骨、滑膜和3例未累及关节的创伤患者正常关节软骨和滑膜 HMGB1的表达规律与分布特点及其与 C 反应蛋白(CRP)的关系。结果 42例OA 中,35例软骨 HMGB1染色阳性,占83.3%;30例滑膜 HMGB1染色阳性.占71.4%,其表达以胞浆分布为主,胞核中较少,3例正常关节软骨和滑膜 HMGB1标记均为阳性。其表达以胞核分布为主,胞浆中极少分布。OA 患者关节软骨和滑膜 HMGB1细胞内分布与关节正常者有明显的不同。OA 患者 HMGB1阳性的软骨细胞数占软骨细胞总数的70.2%,HMGB1阳性的滑膜上皮细胞数占滑膜上皮细胞总数的60.5%,与关节正常者比较,差异无统计学意义(P>0.05)。OA 患者外周血CRP 含量[(20.4±16.7)ng/L]明显升高(P<0.01)。结论 OA 患者关节软骨及滑膜中核外HMGB1可能在 OA 组织损伤的病理过程中发挥作用,OA 患者关节软骨及滑膜上皮细胞中核外HMGB1作为晚期炎症因子参与了 OA 的疾病过程。     

Effect of dehydroepiandrosterone on cartilage and synovium of knee joints with osteoarthritis in rabbits

The aim of this study was to investigate the effects of intra-articular injection of dehydroepiandrosterone (DHEA) on cartilage and synovium of knee joints with osteoarthritis (OA) in rabbits and the underlying mechanism. Forty rabbits underwent unilateral anterior cruciate ligament transaction and were divided into two groups. Rabbits were injected with 100 μmol/l DHEA dissolved in the dimethylsulphoxide (DMSO) in the knee joints 5 weeks after transaction, once a week for 5 weeks. Rabbits injected with DMSO under the same condition were served as a control. All rabbits were killed 1 week after the last injection. The knee joints were evaluated by gross morphology, histology, and gene expression analysis. Gross morphologic inspection and histological evaluation showed that the DHEA group appeared less damage in cartilage and synovium as compared with the control. Gene expression analysis revealed that the mRNA expression of matrix metalloproteinase-3 (MMP-3) in cartilage and synovium decreased significantly in the DHEA group and that of tissue inhibitor of metalloproteinase-1 (TIMP-1) increased. No significant difference of interleukin-1 beta (IL-1β) mRNA expression was found in the cartilage between two groups while the mRNA expression of IL-1β in the synovium was largely suppressed in the DHEA group. The study suggests that DHEA plays a protective role against cartilage degradation and synovium inflammation in rabbits with OA. This role may be achieved through the regulation of the MMP-3, TIMP-1, and IL-1β gene expression in the cartilage and synovium.     

Occurrence of interleukin-1 in human synovial fluid: detection by RIA,bioassay and presence of bioassay-inhibiting factors

Summary Synovial fluid (SF) from patients with osteoarthritis (OA), rheumatoid arthritis (RA), and various other arthridites was analyzed to assess the prevalence of interleukin-1 (IL-1) using both radioimmunoassay competitive inhibition specific for the beta form of IL-1 and the D10.G4.1 cell line bioassay which measures both alpha and beta forms of IL-1. Using radioimmunoassay competitive inhibition, IL-1 was found in 45% and 60% of individual samples from patients with OA and RA respectively. When RA and OA SF were examined in sequentially obtained samples, IL-1 occurred in one or more samples from 8 of 10 patients studied, suggesting the probability that it can be produced at some time in SF by all patients with these conditions. No correlation between SF leukocyte counts and the occurrence of IL-1 was noted and no effect of antiinflammatory drug treatment on the prevalence of IL-1 was found. When tested for the presence of IL-1 by the D10.G4-1 cell line, 66% and 50% of RA and OA patients respectively were found to contain IL-1. These were not in total concordance with results obtained by RIA. Of all SF tested, seven were negative by RIA but positive by D10.G4.1 and these are considered to contain IL-1. Seven samples which were RIA positive and D10.G4.1 negative were tested for their ability to inhibit IL-1 responses in the bioassay. Five of these contained inhibitor and one markedly enhanced the proliferative response of D10.G4.1 to a known amount of IL-1. The inhibitors and the non-IL-1 enhancing factor have yet to be characterized.     

Dermatan sulfate in the synovial fluid of patients with knee osteoarthritis

Biochemical factors play an important role in osteoarthritis (OA) pathogenesis. The purpose of this study is to clarify whether the dermatan sulfate (DS) levels in the synovial fluid of patients with knee OA are related to residual cartilage. Synovial fluid was obtained from 51 OA patients. Knee radiographs were evaluated with the Kellgren–Lawrence (K/L) grading scale. The levels of the following disaccharides were measured by high-performance liquid chromatography (HPLC): DS (DSΔDi4S), chondroitin 6-sulfate (CSΔDi6S), and chondroitin 4-sulfate (CSΔDi4S). The concentration of cartilage oligomeric matrix protein (COMP) was measured by a sandwich ELISA. The levels of DSΔDi4S in Grades 0 and I OA were significantly higher than levels in Grade II (P = 0.0458), Grade III (P < 0.0001) and Grade IV (P < 0.0001), and we found strong relationships between the levels of DSΔDi4S and those of CSΔDi6S (P < 0.0001, r = 0.705), CSΔDi4S (P < 0.0001, r = 0.750), and COMP (P < 0.0001, r = 0.699). We conclude that the presence of DSΔDi4S reflects proteoglycan metabolism in the residual articular cartilage of OA patients. This suggests that metabolism of the small leucine-rich repeat proteoglycans decorin and biglycan, which contain chains of DSΔDi4S, is similar to that of aggrecan.     

Expression of CD44 in articular cartilage is associated with disease severity in knee osteoarthritis

Abstract

Objectives To investigate CD44 levels in articular cartilage of knee osteoarthritis (OA) and the relationship between CD44 and severity of the disease.

Methods All 50 cartilage tissues included normal and OA cartilage, and were ascribed to the following four groups on the basis of modified Mankin score: normal, mild lesions, moderate lesions and severe lesions. CD44 levels in articular cartilage were assessed by immunohistochemical methods.

Results CD44 levels were detected in all four groups. The difference in average gray value of CD44 expression showed statistical significance when compared between each group (P < 0.05). In addition, CD44 expression in each group correlated with disease severity, according to the modified Mankin score (ρ = ?0.848, P < 0.01).

Conclusions CD44 in articular cartilage is associated with progressive knee OA joint damage.     

Immunoglobulin G and serum albumin isolated from the articular cartilage of patients with rheumatoid arthritis or osteoarthritis contain covalent heteropolymers with proteoglycans

Summary The present study was undertaken to identify the cartilage matrix molecules that are bound with intermolecular disulfide bonds to IgG and serum albumin molecules recovered from the articular cartilage of patients with rheumatoid arthritis (RA) or osteoarthritis (OA). The cartilage specimens were extracted sequentially with three changes of neutral buffer, three changes of 6 M guanidine hydrochloride and then partiallydegraded with bacterial collagenase. The extracted IgG and albumin, along with matrix molecules bound to these proteins, were isolated with affinity chromatography using antibodies to IgG or human serum albumin conjugated to agarose beads. The isolated materials were characterized with sodium dodecyl sulfate polyacrylamide gel electrophoresis and transfer blotting, using specific antibodies to IgG, albumin, and proteoglycans. In the isolated materials, heteropolymers with IgG or albumin wer identified. These polymers contained keratan sulfate and less frequently chondroitin-4-sulfate and chondroitin-6-sulfate. These findings identified the keratan sulfate rich proteoglycans, prevalent at the surface of joint cartilage, as the most common cartilage matrix molecules that are covalently bound to IgG or to serum albumin by disulfide bonds in the articular cartilage of patients with RA or OA.     

骨关节炎患者血清和滑液中金属蛋白酶-2和-9的研究

目的 探讨金属蛋白酶－2和－9与骨关节炎实验室指标和膝关节X线分级的相关必,以了解两者的骨关节炎发病中的作用。方法 应用酶谱分析法研究血清和滑液中金属蛋白酶－2和－9的活性,同时检查有关实验室指标及膝关节X线。实验对象为39例膝骨关节炎患者,对照组包括类风湿关节炎68例、强直性脊柱炎79例和反应性关节炎39例以及正常人14例。结果 在实验组和各关节炎对照组所有血清及滑液标本中金属蛋白酶－9和－2酶原活性均比正常对照组显著增强,骨关节炎滑液中金属蛋白酶－9酶原活性与其活性形式的活性呈正相关（r=0.656,P=0.038）。金属蛋白酶－2酶原及其活性形式与骨关节炎无相关。结论 金属蛋白酶－9酶原及其活性形式可能是反映关节局部炎症的标志物,与骨关节炎关节软骨破坏有关。     

Changes in cartilage proteoglycan aggrecan after intra-articular injection of interleukin-1 in rabbits: studies of synovial fluid and articular cartilage.

OBJECTIVE: To determine how acute but transient inflammation affects the cartilage proteoglycan aggrecan and the value of analyses of synovial fluid to study this. METHODS: For 96 hours after a single intra-articular injection of rabbit knees with human interleukin-1 alpha (IL-1 alpha) or vehicle, articular cartilage and synovial fluid were examined using a putative indicator of aggrecan synthesis (aggrecan chondroitin sulphate epitope 846), immunoreactive keratan sulphate, and total glycosaminoglycan (GAG) content. Aggrecan extractability (with 0.5 M NaCl) followed by 4 M guanidine hydrochloride extraction permitted analyses of cartilage damage, total content and aggrecan heterogeneity. Aggrecan epitopes as well as GAG were assayed in synovial fluid. Changes were related to total joint leucocyte content in synovial fluid. RESULTS: At 10 ng, IL-1 alpha produced a transient increase in synovial fluid leucocytes at six hours and 24 hours. This accompanied a reduction in content and increased extractability of GAG, which was greatest in the tibial medial compartment of the knee. Further studies of this compartment showed no change in keratan sulphate epitope content, but a transient increase in extractability in 0.5 M NaCl. Epitope 846 content and extractability were unchanged. Total contents and extractability for GAG were inversely correlated in both controls and joints injected with IL-1 alpha. These changes were accompanied by transient increases in GAG, keratan sulphate epitope, and 846 content in synovial fluid. CONCLUSION: According to the aggrecan component measured, damage to the matrix of articular cartilage was sometimes reflected by a transient increased extractability and a net loss of aggrecan. There was always an increased release of GAG, and keratan sulphate, and 846 epitopes into synovial fluid. These studies show that changes in aggrecan epitopes and GAG in synovial fluid reflect changes in cartilage metabolism induced by acute transient inflammation.