高压氧治疗对严重烧伤患者血中sIL-2R和Fn含量变化的影响

目的通过观察高压氧治疗(Hyperbaric Oxygen Therapy,HBOT)对烧伤患者血中可溶性白介素2受体(Soluble interleukin-2 receptor,sIL-2R)及纤维连接蛋白(Fibronectin,Fn)含量的影响,探讨 HBOT 防治烧伤感染的价值。方法选择42例严重烧伤患者(烧伤面积>30%或Ⅲ度面积>10%),随机分为 HBOT 组(25例)和非 HBOT 组(17例),另选40名健康献血员作正常对照组。于伤后8h 及1,2,3,5,7,10,14,17,21,28,35天采集静脉血,ELISA 法测定血清 sIL-2R,火箭免疫电泳法测定其血浆 Fn,同时观察两组患者脓毒症发生率。结果非 HBOT 组:与正常对照组相比,伤后各时相点血清 sIL-2R 水平显著升高,而血浆 Fn 含量明显降低(P<0.05或 P<0.01);HBOT 组:与正常对照组相比,除伤后21天外,其余各时相点血清 sIL-2R 升高不明显;除伤后8h外,其余各时点血浆 Fn 降低不明显(P>0.05)。但与非 HBOT 组相比,伤后各时相点血清 sIL-2R均显著降低,而血浆 Fn 则明显增高(P<0.05或 P<0.01);与此同时,脓毒症发生率亦明显降低(P<0.05)。结论 HBOT 可显著降低严重烧伤患者血清 sIL-2R,而明显增高血浆 Fn,故对防治烧伤感染可能有益。     

选择性脾胃区减断分流术对血清IL-4,IL-6和sIL-2R水平的影响

目的探讨门静脉高压症脾功能亢进患者行选择性脾胃区减断分流术(selective decongestive devascularization shunt of gastrosplenic region,SDDS-GSR)后血清白介素-4(Interleukin-4,IL-4)、白介素-6(Interleukin-6,IL-6)和游离白介素-2受体(soluble interleukin-2 receptor,sIL-2R)水平的变化及意义。方法ELISA法检测8例SDDS-GSR术后1～3年门脉高压症患者血清IL-4,IL-6和sIL-2R水平,并与正常人及门脉高压症非手术患者作对照研究。结果门脉高压症非手术患者血清IL-4,IL-6和sIL-2R水平分别为(15.67±3.15)pg/ml,(3.16±1.30)pg/ml和(161.03±30.61)pg/ml,较正常组显著升高(P<0.01),SDDS-GSR术后IL-6,sIL-2R水平分别为(2.11±0.59)pg/ml和(124.98±36.93)pg/ml,较非手术组降低有统计学意义(P<0.05),但仍显著高于正常组(P<0.05)。结论IL-6和sIL-2R的分泌调节紊乱在肝硬化发病机制中起重要作用,SDDS-GSR术可有效缓解脾亢,显著降低患者血清IL-6和sIL-2R水平,表明有利于肝功能的维护和缓解肝硬化进展。     

羟乙基淀粉溶液对手术病人血浆细胞因子的影响

目的 观察羟乙基淀粉对手术病人免疫功能的影响。方法 40例病人分为两组，分别于术前静脉输注10%羟乙基淀粉或复方乳酸钠溶液，用夹心法ELISA检测病人术前和术后血浆中可溶性白细胞介素-2受体（sIL-2R)，白细胞介素-6（IL-6），白细胞介素-8（IL-8），肿瘤坏死因子-α（TNF-α）的浓度和粒细胞集落刺激因子（G-CSF）阳性率。结果 所有病人术后血浆中sIL-2R,IL-6,IL-8,TNF-α的浓度和G-CSF阳性率均明显增加，但复方乳酸钠溶液组的增加幅度明显高于羟乙基淀粉组。结论 术前输注羟乙基淀粉溶液能够有效地减轻手术和麻醉导致的病人机体免疫功能的抑制。     

食管癌患者外周血Th1/Th2及细胞因子表达的变化

目的 观察食管癌患者机体免疫状态的变化.方法 采用流式细胞技术检测65例哈族患者T淋巴细胞亚群(Th1、Th2、CD3+、CD4+、CD8+细胞),采用双抗体夹心酶联免疫吸附试验(ELISA)法检测血清中自细胞介素(IL)-2、干扰素(IFN)-γ、IL-4、IL10、sIL-2R和肿瘤坏死因子(TNF)-β水平.结果 食管癌患者外周血Th1/Th2细胞比值降低(P<0.05),其中Th1细胞表达的IL-2、IFN-γ等细胞因子水平低于正常对照组;Th2细胞表达的IL-4、IL10细胞因子水平高于正常对照组(P<0.05).T细胞介导的细胞免疫及血清sIL-2R和TNF-β水平存在改变和紊乱,其程度与肿瘤TNM分期相关,其特征为:CD3+、CD4+细胞减少(P<0.05),而CD8+细胞增加(P<0.01);CD4+/CD8+细胞比值下降(P<0.01),血清sIL-2R和TNF-β水平升高(P<0.05).食管癌根治术后1个月CD3+、CD4+细胞回升,CD8+细胞回降,同时血清sIL-2R和TNF-β水平降低(P<0.01).结论 食管癌患者外周血Th1/Th2细胞比值降低,细胞因子表达失衡,患者存在免疫功能抑制.     

奥曲肽对兔肝脏缺血-再灌注损伤的保护作用

目的 研究奥曲肽对兔肝脏缺血再灌注(I-R)损伤的保护作用.方法 24只新西兰大白兔随机均分为肝脏I-R组(R组)、奥曲肽预适应组(T组)和假手术组(C组).观察三组肝门阻断前(T1)、阻断后15 min(T2)、30 min(T3)、再灌注15 min(T4)、30 min(T5)、60 min(T6)、120 min(T7)、240 min(T8)的MAP和HR变化及T1、T3、T5、T6、T7、T8各时点丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)、内毒素(ET)以及肿瘤坏死因子α(TNF-α)、白细胞介素-1β(IL-1β)的变化.结果 R组T2～T6、T组T2～T4时MAP明显低于、HR明显慢于C组(P<0.05),R组在T2～T6时MAP明显低于、HR明显慢于T组(P<0.05);T3、T5～T8时,R、T两组ALT、AST、LDH、ET均明显高于C组(P<0.05);R组明显高于T组(P<0.05),R组T3、T5～T8、T组T5～T8日血浆TNF-α、IL-1β明显高于C组(P<0.05),且T组T3、T7、T8时血浆TNF-α明显低于R组,T5、T6时明显高于R组(P<0.05).T组T3、T5～T8时血浆IL-1β明显低于R组(P<0.05).结论 奥曲肽对兔肝脏1-R损伤有明显的保护作用,其机制可能与下调TNF-α、IL-1β等炎性介质和降低血浆中ET水平有关.     

梗阻性黄疸患者手术前后sIL—2R水平的动态观察

目的探讨梗阻性黄疸(梗黄)患者围手术期血清可溶性白细胞介素-2受体(sIL-2R)水平的变化及意义.方法应用双抗体夹心(ELISA)法检测30例梗黄患者手术前后血清sIL-2R的水平. 结果梗黄患者血清sIL-2R明显高于正常组,其表达分别与梗阻程度、梗阻时间和营养状况呈显著正相关(r=0.734, P<0.01; r=0.646, P<0.01; r=0.594, P<0.05 ).恶性梗阻性黄疸(恶性梗黄)组术前血清sIL-2R显著高于良性梗阻性黄疸(良性梗黄)组(P<0.05)和正常对照组(P<0.01); 恶性梗黄组中有转移者,血清sIL-2R水平显著高于无转移者(P<0.05).围手术期免疫功能呈现暂时抑制到逐渐恢复的过程,术后第21天,良性梗黄患者血清sIL-2R恢复到正常水平,而恶性梗黄患者则仅恢复到术前水平.结论梗黄患者存在免疫抑制,其血清sIL-2R异常表达与梗阻类型、梗阻程度、梗阻时间、营养状况以及是否转移有关.检测梗黄患者血清sIL-2R可作为其免疫状况评价、病情、治疗和预后评估的有用指标.     

食管癌患者外周血sFas及sIL-2R表达的研究

目的:探讨食管癌患者外周血中sFas及sIL-2R的变化规律及其临床意义。方法:采用ELISA双抗体夹心法对28例食管癌患者手术前后外周血中sFas及sIL-2R进行检测,并与20例正常人进行对比研究。结果:食管癌患者外周血中sFas浓度高于正常对照,且术前高于术后,但无显著差异(P>0.05)。食管癌患者外周血中sIL-2R浓度显著高于正常对照(P<0.05),且其术后较术前水平降低。结论:外周血中sIL-2R和sFas可间接反映膜分子IL-2R和Fas表达的高低,检测外周血中sIL-2R和sFds有助于判断食管癌患者的免疫功能状态及预后。     

慢性乙型肝炎患者阿德福韦酯治疗前后血清Th1和Th2细胞因子水平变化及其与HBeAg的关系

目的 观察HBeAg阳性慢性乙型肝炎患者阿德福韦酯治疗前后不同时相点血清IFN-γ和IL-4水平及其与HBeAg的关系,探讨阿德福韦酯治疗对机体免疫状态的影响.方法 采集30例阿德福韦酯治疗前、治疗16周、52周和132周患者血清,其中完全应答组14例,部分应答组16例及健康对照组10例,ELISA检测IFN-γ和IL-4水平,乙型肝炎病毒血清标志物定量检测采用美国Abbott公司微粒子酶免疫法,HBeAg≤1.0 S/CO为阴性,抗-HBe ≤1.0 S/CO为阳性.结果 完全应答组各时相点IFN-γ水平显著高于部分应答组(P＜0.05)及正常对照组(P＜0.05),部分应答组与健康对照组相比无显著差异(P＞0.05);完全应答组IL-4水平在治疗后逐渐下降,部分应答组变化不大;各组在治疗前HBeAg水平与IFN-γ及IL-4水平均无明显相关性;完全应答组在治疗后各时相点HBeAg水平下降,且与IFN-γ升高程度呈负相关、与IL-4水平下降程度呈正相关,与部分应答组相比有显著差异(P＜0.05).结论 阿德福韦酯治疗后慢性乙型肝炎患者细胞免疫应答有一定程度的恢复,其恢复程度与HBeAg水平下降幅度呈正相关.     

CXCL8,CXCL10和Th1/Th2细胞因子在神经梅毒患者的血清和脑脊液中的表达情况研究

目的:旨在调查趋化因子8和10(CXCL8和CXCL10)、Th1细胞因子(IL-2,IL-12和IFN-γ)和Th2细胞因子(IL-6和IL-10)在神经梅毒患者血清和脑脊液中(CSF)的含量,阐明CXCL8,CXCL10和Th1/Th2细胞因子在神经梅毒的免疫应答和发病机制中的作用。方法:应用酶联免疫吸附法检测42例神经梅毒患者(22例男性,20例女性),44例梅毒组(23例男性,21例女性)和40例对照组(20例男性,20例女性)的血清和CSF中CXCL8,CXCL10,IL-2,IL-12,IFN-γ,IL-6和IL-10的含量。结果:神经梅毒患者的血清中CXCL8,CXCL10,IL-2,IL-12,IFN-γ,IL-6和IL-10含量显著低于梅毒组和对照组(P<0.05)。其中,这些因子在男性神经梅毒患者中的含量显著低于其在女性神经梅毒患者中的含量(P<0.05)。然而,神经梅毒患者的CSF中CXCL8,CXCL10,IL-2,IL-12,IFN-γ,IL-6和IL-10含量显著高于梅毒组和对照组(P<0.05)。同样,这些因子在男性神经梅毒患者中的含量显著高于其在女性神经梅毒患者中的含量(P<0.05)。结论:神经梅毒患者存在细胞免疫功能障碍,神经梅毒患者的免疫应答涉及CXCL8、CXCL10和Th1/Th2细胞因子。     

氟比洛芬酯对喉癌喉裂开术患者围术期细胞因子及术后疼痛的影响

目的 观察氟比洛芬酯对喉癌喉裂开术患者术后疼痛及围术期细胞因子的影响.方法 择期行喉癌喉裂开术患者60例,随机均分为三组:术毕前10 min分别静脉注射氟比洛芬酯1.0mg/kg(F<,1>组)、氟比洛芬酯1.5 mg/kg(F<,2>组)、生理盐水5 ml(C组).VAS评分评定术后1、2、4、68、12、24 h的疼痛程度.监测术前、术毕和术后6、24 h血浆白细胞介素(11)-2、可溶性白细胞介素-2受体(SIL-2R)、IL-6、IL-10的浓度.结果 与术前比较,C组SIL-2R水平在术后6 h明显降低、术后24 h明显升高;F<,1>、F<,2>组SIL-2R水平明显降低;三组IL-6、IL-10水平明显升高和IL-2水平明显降低(P<0.05).与C组比较,术后1、2、4 h时F<,2>组VAS明显降低,术后4 h时F<,1>组VAS明显降低(P<0.05);术后6、24 h时F<,1>、F<,2>组的IL-10水平和术后24 h时的IL-2水平明显升高,且F<,2>组明显高于F<,1>组(P<0.05);F<,1>、F<,2>组在术后6 h时的IL-6水平和术后6、24 h时SIL-2R水平明显降低,且F<,2>组明显低于F<,1>组(P<0.05).结论 1.5 nag/kg氟比洛芬酯能有效地平衡细胞因子,缓解术后的免疫损伤,具有免疫保护作用.     

肾移植后血清白细胞介素2、可溶性白细胞介素2受体和白细胞介素6的监测

动态监测６０例肾移植患者术后２个月内血清白细胞介素２（ＩＬ－２）、可溶性ＩＬ－２受体（ｓＩＬ－２Ｒ）和白细胞介素６（ＩＬ－６）的变化。结果发现发生急性排斥反应时，上述细胞因子的升高较临床诊断提早数天，并且显著高于环孢素Ａ肾中毒组；对甲泼尼龙敏感的排斥反应，抗排斥治疗数天后上述因子下降到排斥前水平。提示肾移植术后动态监测患者血清ＩＬ－２、ｓＩＬ－２Ｒ和ＩＬ－６有助于急性排斥反应的早期诊断、鉴别诊断、及时治疗和甲泼尼龙抗排斥的疗效评价。     

同种异体双手移植术细胞因子的动态监测

目的探讨同种异体双手移植术细胞因子动态监测的临床应用价值.方法 2000年9月～11月,采用ELISA法动态监测异体手移植术患者移植前后,血清中可溶性白细胞介素-2受体(solube interleukin-2,receptor,sIL-2R)、白细胞介素-2(interlukin-2,IL-2)和白细胞介素-6(IL-6)水平的变化,并与15名健康对照血清中相应细胞因子水平进行比较.结果血清IL-2和IL-6水平于术后诱导期明显下降,与术前比较有统计学意义(P＜0.05),而后回升,在维持期保持较术前略高水平,与诱导期比较有统计学意义(P＜0.05);sIL-2R水平术后明显上升,并维持于较高水平.血清IL-2水平与对照组比较,在移植前后均有统计学意义(P＜0.01);IL-6水平与对照组比较,术后诱导期有统计学意义(P＜0.05).结论血清IL-2、IL-6和sIL-2R的动态监测可能有助于排斥反应的诊断,以及预防机会性感染、肿瘤及移植物抗宿主疾病的发生.     

严重创伤患者白细胞介素—2及其受体变化与多器官功能障碍综合 …

目的 探讨血清白介素－２（ＩＬ－２）与可溶性白介素－２受体（ｓＩＬ－２Ｒ）在创伤后多器官功能障碍综合征（ＭＯＤＳ）发生、发展中的作用机制。方法 应用ＥＬＩＳＡ法动态监测５９例严重创伤患者血清ＩＬ－２与ｓＩＬ－２Ｒ水平变化,比较ＭＯＤＳ与非ＭＯＤＳ组间ＩＬ－２、ｓＩＬ－２Ｒ变化之差异。结果 ５９例患者血甭ｓＩＬ－２Ｒ水平显著升颃是ＩＬ－２明显下降,且升 峰值与降低之谷值在ＭＯＤＳ组更为明显,与非ＭＯ     

血清sIL-2R、IL-6及胆汁IL-6监测对早期预测肝移植急性排斥反应的作用

目的　评价血清sIL 2R、IL 6及胆汁IL 6水平在预测肝移植急性排斥反应中的意义。方法　连续 3周监测 2 8例肝移植受者术后血清sIL 2R、IL 6及胆汁IL 6水平 ,观察其与急性排斥反应的关系。结果　在急性排斥反应 (AR)组 ,血清sIL 2R及胆汁IL 6水平在排斥发作时明显升高 ,与非排斥组比较有显著性差异 (P <0 .0 1)。当AR经激素冲击治疗逆转后 ,血清sIL 2R及胆汁IL 6下降至排斥前的水平。在AR组 ,仅有 3例受者在排斥发作时血清IL 6水平升高 ,与非排斥组相比 ,血清IL 6水平无明显差异 (P >0 .0 5 )。结论　胆汁IL 6水平有望作为预测AR敏感、较具特异性及非侵袭性的手段。同时 ,其水平还可作为观察抗排异治疗是否有效的指标。     

Correlation of estradiol, parathyroid hormone, interleukin-6, and soluble interleukin-6 receptor during the normal menstrual cycle

Rodent models suggest that estradiol deficiency promotes bone loss through increasing interleukin-6 (IL-6) activity. However, it is controversial as to whether these findings are applicable to humans. To evaluate estradiol-mediated modulation of IL-6 activity in relation to bone metabolism in humans, we measured serum IL-6, soluble interleukin-6 receptor (sIL-6R), estradiol (E2), progesterone, luteinizing hormone, follicle-stimulating hormone, intact parathyroid hormone (PTH), serum and urine Ca, and bone biochemical markers (serum bone-specific alkaline phosphatase, osteocalcin, and serum and urine deoxypyridinoline [Dpd]) across one menstrual cycle for 211 women. Neither IL-6 nor sIL-6R levels differed between the follicular phase (FP) and the luteal phases (LP). However, IL-6 was negatively correlated with E2 during the FP (p =0.003). Furthermore, IL-6 correlated positively with serum Ca over the entire cycle (p = 0.0091. Serum Ca correlated positively with serum (p = 0.040) and urine (p = 0.006) Dpd. PTH was significantly higher during the FP than in the LP (p = 0.004). PTH was negatively related to E2 (p = 0.002), serum Ca (p < 0.001), and urine Ca (p = 0.036), whereas it was positively correlated with IL-6 (p = 0.027). These data demonstrate that IL-6 and PTH fluctuate with E2, and serum II-6 is associated with PTH levels during the menstrual cycle. However, the role of 11-6 in bone remodeling during the normal menstrual cycle remains to be determined.     

Circulating levels of interleukin-6 and its soluble receptor in patients with head injury and fracture

There is evidence that fractures heal more rapidly in patients with head injury. We measured the circulating level of interleukin-6 (IL-6) and its soluble receptor (sIL-6R) and soluble glycoprotein 130 (sgp130) in serum from patients who had sustained a head injury with and without fracture and compared these with levels found in control subjects. Within 12 hours of injury the serum level of IL-6 was significantly higher in patients with head injury and fracture compared with the control group. Levels of IL-6 were also significantly higher in patients with head injury and fracture compared with fracture only. While there was no significant difference in circulating levels of sIL-6R in the initial samples they were increased one week after surgery in patients with head injury and fracture and with head injury only. In addition, reduced levels of sgp130 in patients with head injury with and without fracture indicated a possible reduction of the inhibitory effect of this protein on the activity of IL-6. Our study suggests that IL-6 may be involved in altered healing of a fracture after head injury.     

Elevated serum levels of soluble interleukin-4 receptor in osteoarthritis

OBJECTIVE: To test the importance of the interleukin-4 (IL-4)/IL-4 receptor (IL-4R) system in osteoarthritis (OA) we evaluated soluble IL-4R (sIL-4R) levels in sera of patients with different forms of OA and healthy individuals. METHODS: We recruited: 141 patients with hand OA, 70 with nodal and 71 with erosive hand OA; 64 patients undergoing total joint replacement, 34 with hip and 30 with knee OA; and 38 ethnically and geographically age-matched healthy individuals [normal controls (NC)]. RESULTS: Serum sIL-4R concentration was found to be significantly higher in all OA patients than that in NC. When patients were divided into four subgroups (nodal, erosive, hip and knee OA) significant differences were present when comparing NC with each subgroup. This was true also when small-joint OA groups were compared with large-joint OA groups, the latter being associated with higher IL-4R levels. CONCLUSIONS: We found increased levels of sIL-4R in OA patients compared with healthy individuals. We speculate that this reduces availability of IL-4, and its effects on chondrocytes.     

Plasma soluble interleukin-2 receptor levels during and after upper abdominal surgery

Soluble interleukin-2 (IL-2) receptor (sIL-2R) is reported to be up-regulated in inflammatory disorders. Although sIL-2R may modulate perioperative inflammatory responses, it remains unclear whether upper abdominal surgery affects plasma sIL-2R levels. We evaluated the influence of major abdominal surgery on plasma sIL-2R levels. Ten patients scheduled for upper abdominal surgery received anaesthesia with isoflurane, nitrous oxide, and epidural block. Plasma sIL-2R and IL-6 levels were determined at pre-anaesthesia, 0, 2, and 4 hours during surgery, and on postoperative days 1 (POD1) and 3 (POD3). The plasma levels of sIL-2R decreased significantly and achieved their minimum value at 4 hours (677.0 +/- 125.3 pg/ml, P < 0.01 compared to pre-anaesthesia value; 924.5 +/- 178.8 pg/ml, 95% confidence interval = 122.2-550.4). The plasma sIL-2R levels increased on POD1 (1336.5 +/- 174.0 pg/ml) and POD3 (1629.0 +/- 262.8 pg/ml), and reached a level significantly higher than the baseline (P < 0.05 and P < 0.001, 95% confidence interval = 93.4-730.6 and 402.8-1006.2, respectively). The plasma sIL-2R levels on POD3 significantly correlated with the peak IL-6 levels (r = 0.67, P < 0.05). The plasma sIL-2R levels on POD3 correlated with the amount of intraoperative bleeding (r = 0.66, P < 0.05). In conclusion, we found that major abdominal surgery induces characteristic changes in plasma soluble IL-2 receptor levels.     

Soluble Interleukin-2 Receptor Levels in Hepatocellular Cancer: a More Sensitive Marker Than Alfa Fetoprotein

Background: Worldwide, the majority of cases of hepatocellular cancer (HCC) arise in individuals with chronic hepatitis B or C virus infections. Early detection of HCC in these patients provides the best chance for curative treatment, but serum alfa fetoprotein (AFP) levels are frequently normal in patients with small HCCs. The purpose of this study was to determine: (1) whether soluble interleukin-2 receptor (sIL-2R) levels are elevated more frequently than AFP levels in HCC patients and (2) whether sIL-2R levels are useful as a marker of successful treatment and recurrence of disease.Patients and Methods: We are performing a prospective screening program with high-risk, chronic hepatitis virus-infected patients to detect HCC. Patients are screened by using abdominal ultrasonography, serum AFP measurements, and serum sIL-2R measurements. Normal serum sIL-2R levels were established using results from 174 healthy volunteers with no evidence of hepatitis virus infection or HCC.Results: HCC has been diagnosed in 99 patients from a cohort of 1520 screened patients. Serum AFP levels were elevated in 79 patients (80%), whereas sIL-2R levels were elevated in 98 of the 99 patients (99%, P < .01, ² test). For 27 of the 99 patients (27%), HCC was diagnosed at an early stage and complete resection or ablation was performed. Serum sIL-2R levels returned to normal in all 27 patients after treatment, whereas AFP levels remained slightly elevated in 5 of the 27 (18%). Among the 16 patients in this group of 27 who developed recurrent HCC, sIL-2R levels became elevated in all 16, whereas AFP levels were elevated at diagnosis of recurrence for only 10 (P < .05).Conclusions: This study with chronic hepatitis B or C virus-infected patients indicates that (1) serum sIL-2R levels are abnormal in patients with HCC with a significantly greater frequency, compared with AFP levels, and (2) sIL-2R levels are a more sensitive marker of successful treatment and recurrence of HCC. Based on these findings, we now use serum sIL-2R measurements both to screen high-risk patients and to monitor treatment responses in patients with hepatitis who develop HCC.Presented at the 51st Annual Cancer Symposium of The Society of Surgical Oncology, San Diego, California, March 1998     

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.