全髋关节置换术后血清炎性因子表达特点及临床意义

目的：研究血清炎性因子白介素1（IL1）、白介素2（IL2）、白介素6（IL6）及白介素10（IL10）在人工全髋关节置换术后变化特点及意义。方法：自2010年2月至6月,选择初次行单侧人工全髋关节置换术的30例股骨头无菌性坏死患者,男18例,女12例;年龄52～70岁,平均（58.4±6.6）岁;FicatⅡ型20例,Ⅲ型10例。分别在术前第1天及术后第1、3天用放射免疫方法检测IL1、IL2、IL6及IL10,同时检测C反应蛋白,对结果进行统计学分析。结果：人工全髋关节置换术后第1天患者血清中IL1、IL6和IL10值均较术前升高（t=2.62,3.51,2.21,P〈0.05）,在术后1～3d达到高峰,3d后开始降低。患者血清IL2水平术后降低（t=2.16,P〈0.05）,后逐渐升高。结论：全髋关节置换术后3d是抗炎治疗的关键,术后及时监测IL1、IL2、IL6及IL10的变化,同时观察临床症状,可更敏感地掌握患者的治疗效果,预测病情发展。     

Whole blood production of monocytic cytokines (IL-1beta, IL-6, TNF-alpha, sIL-6R, IL-1Ra) in haemodialysed patients.

BACKGROUND: The production of monocytic cytokines by isolated mononuclear cells after stimulation by phytohaemagglutinin (PHA) and lipopolysaccharide (LPS) is generally increased in haemodialysed (HD) patients. We performed whole blood (WB) cultures to evaluate cytokine production by blood cells inside their complex cellular and humoral network. METHODS: Diluted whole blood from HD patients (collected before dialysis) and controls was cultured alone with PHA (2.5 microg/ml) or LPS (1 and 3 microg/ml). Supernatants were collected after 24 and 48 h of culture, and concentrations of IL-1 beta, IL-6, TNF-alpha, sIL-6R and IL-1Ra were determined by ELISA. RESULTS: The low spontaneous production of IL-1beta, IL-6 and TNF-alpha in both patients and controls was not significantly modified by PHA. The lower dose of LPS (1 microg/ml) induced a significant but lower increase in production of IL-1beta, IL-6 and TNF-alpha in patients than in controls. In contrast, while it did not further increase their production in controls, the higher concentration of LPS (3 microg/ml) still increased their production in patients to the same level than in controls. The plasma concentrations of sIL-6R were higher in patients than in controls. In both groups, the sIL-6R concentration did not vary during the culture period whether the cells were stimulated or not with LPS or PHA. This suggests that the increased plasma levels of sIL-6R were not produced by blood cells. Despite a similar significant LPS and PHA induced production of IL-1Ra, the IL-1Ra/IL-1beta ratio was always higher in patients than in controls. CONCLUSION: Monocytes from HD patients in WB cultures are hyporesponsive to PHA and LPS for their IL-1beta, TNFalpha and IL-6 production in contrast to isolated monocytes that demonstrate signs of activation. If it reflects the in vivo situation it could partly explain the immune defect in uraemic and haemodialysed patients. Higher sIL-6R/IL-6 and IL-1Ra/IL-1beta ratios could also participate to the complex immune disturbances of HD patients by reducing the biological activity of two cytokines playing a major role in the immune and inflammatory network.     

Effect of proinflammatory cytokines (IL-6, TNF-alpha,IL-1beta) on hemodynamic performance during orthotopic liver transplantation

BACKGROUND: Proinflammatory cytokines (IL-6, IL-1beta, TNF-alpha) released during liver transplantation may affect hemodynamic stability. The aim of the present study was to analyze the association between IL-6, TNF-alpha, and IL-1beta and systemic vascular resistance during the phases of liver transplantation. MATERIAL AND METHODS: The proinflammatory cytokines IL-6, IL-1beta, and TNF-alpha were analyzed in the blood of 20 consecutive patients who underwent transplantation. Blood samples were drawn from the pulmonary artery at serial times during surgery. Hemodynamic parameters were determined using a cardiac output monitor. Correlations between parameters were analyzed using the Spearman's rho and Kendall's tau-b methods. RESULTS: Both in the vena cava and the pulmonary artery, significant association was observed between basal values of IL-6 during hepatectomy and systemic vascular resistance during the phases of liver transplantation: hepatectomy phase (r=.76, P=.02), anhepatic phase (r=.78, P=.03) and reperfusion phase (r=.87, P=.005). CONCLUSIONS: Basal values of IL-6 may be considered a prognostic factor for hemodynamic performance during the phases of liver transplantation.     

IL-1beta, TNF-alpha and IL-6 release from monocytes in haemodialysis patients in relation to dialytic age.

BACKGROUND: It has been suggested that changes in immune response to infectious agents in patients on haemodialysis might be due to impaired monocyte function; uraemic and haemodialysed patients overproduce proinflammatory cytokines, such as interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). METHODS: We quantitated the cytokines released into the plasma and into the supernatants of 24-h cultured purified monocytes, under basal conditions and after stimulation by lipopolysaccharide from Escherichia coli, in 15 healthy subjects (CON), 20 uraemic patients who had not yet started dialysis (CRF) and 60 haemodialysed patients (HD), who were divided into three groups of 20 patients corresponding to short-, medium- and long-term dialysis. RESULTS: Monocytes from HD patients spontaneously secreted significantly higher levels of cytokines than those from controls and uraemic patients who had not yet started dialysis. After stimulation with lipopolysaccharide (LPS), cytokine levels in culture supernatants of cells from HD patients were significantly lower than those from controls and uraemic patients. Moreover, levels of cytokines in monocyte supernatants and plasma from short-, medium- and long-term haemodialysed patients decreased progressively with dialytic age. Monocytes from haemodialysed patients tended to be constitutively active, but their ability to secrete proinflammatory cytokines was inversely correlated with dialytic age. CONCLUSIONS: These results indicate that prolonged treatment with dialysis can be considered a form of chronic stress that causes the progressive activation of monocytes, which ultimately leads to monocyte exhaustion and dysfunction.     

IL-17, IL-1beta and TNF-alpha stimulate VEGF production by dedifferentiated chondrocytes

OBJECTIVE: To verify the involvement of proinflammatory cytokines IL-17, IL-1beta and tumor necrosis factor alpha (TNF-alpha) in cartilage vascularization by stimulating the production of vascular endothelial growth factor (VEGF) by chondrocytes isolated from patients with osteoarthritis (OA), in comparison with patients with rheumatoid arthritis (RA) and patients with femoral or humeral neck fracture (FP). DESIGN: Chondrocytes isolated from patients with OA were maintained in monolayer culture for several passages. Chondrocyte dedifferentiation was monitored by the synthesis of cathepsin B by these cells. Chondrocytes freshly isolated at each subculture (subcultures 1-3) were stimulated with IL-17, IL-1beta or TNF-alpha. Supernatants were collected, immunoassayed for the production of VEGF and cathepsin B and assayed as the source of VEGF on the VEGF sensible ECV304 cell line. The cells were used to quantify intracellular cathepsin B enzymatic activity. RESULTS: In differentiated conditions IL-1beta and TNF-alpha, but not IL-17, can inhibit the spontaneous secretion of VEGF by human OA, RA and FP chondrocytes, and IL-17 can restore the decrease in VEGF secretion caused by TNF-alpha. IL-17, together with IL-1beta and TNF-alpha, can enhance VEGF secretion to various extents by dedifferentiated OA chondrocytes. This change in effect with respect to primary culture was observable for all cytokines at the beginning of dedifferentiation, when the production of VEGF by chondrocytes had dramatically fallen and the cathepsin B synthesis had increased. The amount of VEGF induced by cytokines on dedifferentiated chondrocytes never reached the amount of VEGF produced by differentiated chondrocytes. VEGF produced by chondrocytes stimulated the ECV304 cell line proliferation. CONCLUSIONS: These results indicate that dedifferentiated OA chondrocytes secrete VEGF after stimulation with proinflammatory cytokines. This event may be responsible for neovascularization found in OA cartilage.     

Monitoring of IL-6 levels in patients after total hip joint replacement]

Total hip replacement became a method of choice in treatment of the severe osteoarthritis. Despite the progress in constructing the implants and also the surgical technique, the number of complications rises together with the number of arthroplasties performed. The periprosthetic osteolysis and its consequence--the loosening is the one of the greatest problems of today's joint replacement. It creates the main obstacle for the long-term efficiency of the total hip arthroplasty. It was proved by the numerous research, wear debris of the implant induce the chronic periprosthetic inflammatory process. Many studies emphasize the influence of the proinflammatory cytokines on the bone metabolism. The aim of the study was the evaluation of the inflammatory process in patients with the severe osteoarthritis before the surgery and in subsequent periods after total hip replacements and also in patients with the aseptic loosening of the endoprosthesis, by the monitoring the levels of IL-6 in serum of the peripheral blood. The results suggest, that in patients following THA with the elevated level of IL-6, the inflammatory process was present. This inflammation may lead in future to the aseptic loosening of the implant.     

Influence of pro-inflammatory (IL-1 alpha,IL-6, TNF-alpha,IFN-gamma) and anti-inflammatory (IL-4) cytokines on chondrocyte function

OBJECTIVE: Cytokines produced by inflammatory cells play a pivotal role in synovial inflammation and joint destruction in rheumatoid arthritis. To investigate the influence of pro-inflammatory cytokines (IL-1 alpha, IL-6, TNF-alpha, IFN-gamma) and subsequently the possible beneficial role of an anti-inflammatory cytokine (IL-4) on chondrocyte viability (necrosis/apoptosis), proliferation and nitric oxide (NO) production. METHODS: Primary bovine chondrocytes were cultured until monolayers were obtained. Cells were incubated with cytokines (IL-1 alpha, IFN-gamma, TNF-alpha, IL-4, IL-6) at 0.1, 1, 10 and 100 ng/mL. After 48 h, the viability of the chondrocytes was measured flow cytometrically with propidium iodide. Proliferation was determined by the incorporation of tritiated thymidine. The morphology of the chondrocytes, including presence of apoptotic nuclei, was evaluated by a May-Grünwald-Giemsa staining. In addition, the number of apoptotic chondrocytes was detected flow cytometrically with a TUNEL technique and annexin-V/propidium iodide staining. NO production was evaluated using a spectrophotometric assay, based upon the Griess reaction. RESULTS: The viability and proliferation of bovine chondrocytes decreased after incubation with 100 ng/mL IL-1 alpha, TNF-alpha or IFN-gamma. In contrast, incubation of chondrocytes with IL-4 or IL-6 had no influence on the viability or the proliferation of cells. IL-1 alpha was able to enhance NO production in a dose dependent manner. IFN-gamma and TNF-alpha induced NO production only at the highest concentration (100 ng/mL), whereas IL-4 and IL-6 did not. There was a dose dependent increase in apoptosis of bovine chondrocytes cultured in the presence of IL-1 alpha and TNF-alpha. This effect could not be prevented by preincubation with IL-4. Preincubation with IL-4 diminished IL-1 alpha and TNF-alpha induced NO production and increased proliferation of chondrocytes. In an additional experiment, incubation of human chondrocytes with anti-Fas did not induce apoptosis as measured by annexin-V/propidium iodide staining. CONCLUSIONS: Pro-inflammatory cytokines are able to induce apoptosis, whereas IL-4 as an anti-inflammatory cytokine can inhibit the effect of IL-1 alpha and TNF-alpha on NO production and proliferation of bovine chondrocytes.     

The cytokines IL-1beta and IL-1 receptor antagonist, IL-2 and IL-2 soluble receptor-alpha, IL-6 and IL-6 soluble receptor, TNF-alpha and TNF soluble receptor I, and IL10 in drained and systemic blood after major orthopaedic surgery.

OBJECTIVE: To measure the concentration of the cytokines interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumour necrosis factor-alpha (TNF-alpha) and the modulators of their function interleukin-1 receptor antagonist (IL-1Ra), interleukin-2 soluble receptor alpha (IL-2 sRalpha), interleukin-6 soluble receptor (IL-6sR) and soluble tumour necrosis factor receptor I (sTNFR-I) in systemic and drained blood for the first six hours after a major orthopaedic operation. DESIGN: Prospective study. SETTING: University hospital, Oslo. PATIENTS: 8 patients operated on for thoracic scoliosis. MAIN OUTCOME MEASURE: Concentrations of IL-1beta, IL-2, IL-6, IL-10, TNF-alpha, IL-1Ra, IL-2 sRalpha , IL-6sR, and sTNFR-I were measured together with haemoglobin (Hb) concentration, white cell count (WCC), and differential count in arterial and drained blood at wound closure and 1, 2, 4, and 6 hours postoperatively. RESULTS: IL-1beta and IL-6 concentrations increased significantly in drained blood, whereas that of TNF-alpha increased only in arterial blood. The modulating factors IL-1Ra, sTNFR-I, and IL-10 were increased both in arterial and drained blood. IL-6sR had decreased slightly at 6 hours in drained blood. No IL-2 was found and IL-2 sRalpha decreased simultaneously with the haemodilution. In arterial blood there was a granulocytosis and in drained blood a relative lymphocytosis. CONCLUSION: Cytokine responses to surgical trauma include modulating factors such as soluble receptors and receptor antagonists that have different responses systemically and locally.     

Trasylol (aprotinin) decreases kidney Interleukin-1beta (IL-1beta) and IL-6 levels following renal ischemia and reperfusion injury

Introduction. Acute renal failure (ARF) may be an ominous complication of circulatory arrest in cardiac surgical patients. Aprotinin is used as a therapeutic adjunct to preserving hemostasis by inhibiting protease-mediated fibrinolysis. Aprotinin has been shown to possess anti-inflammatory properties, which may be renal protective. However, it is unknown whether aprotinin decreases renal proinflammatory cytokine production following I/R. Indeed, other agents which have reduced renal IL-1beta and IL-6 have protected renal function in this setting. We hypothesized that aprotinin would decrease renal IL-1beta and IL-6 production following I/R. Methods. Adult male rats were subjected to unilateral I/R with varying lengths of both ischemia and reperfusion, with and without clinically relevant dosing and administration of aprotinin prior to the insult (clinically aprotinin is given prior to circulatory arrest). At various time points, the kidneys were harvested and the tissue homogenates were assayed for IL-1beta and IL-6 (ELISA). All experiments were approved by the Indiana University Animal Care and Use Committee (IACUC). Results. One-hour ischemia and 2 h of reperfusion significantly increased renal tissue IL-1beta and IL-6 levels (P < 0.05 versus sham, ANOVA with Bonferroni/Dunn). Aprotinin significantly (P < 0.05) decreased renal IL-1beta and IL-6 levels at this time point. Aprotinin also significantly decreased renal IL-1beta at the 1 h ischemia/4 h reperfusion time point. At no point did aprotinin increase production of either cytokine. Conclusions. Aprotinin decreases renal proinflammatory cytokine production following I/R. Further study will be needed to determine if aprotinin decreases renal tubular apoptosis and acute renal failure following such conditions. If so, aprotinin may be useful as an adjunct to preserving renal function following diverse planned ischemic events.     

Serum levels of IL-1 beta,TNF-alpha,IL-8, and acute phase proteins in seronegative spondyloarthropathies

OBJECTIVES: Some immunological abnormalities have been described in seronegative spondyloarthropathies (SpA). The aim of this study is to determine the serum levels of IL-1beta, TNF-alpha and IL-8, which are proinflammatory cytokines in active and inactive patients with SpA, to compare the results with those of controls and to investigate a relationship with clinical activity and acute phase proteins. METHODS: Forty-two patients (34 males and eight females) and 22 healthy controls (17 M and 5 F) were included in the study. All patients fulfilled Amor criteria for the classification of SpA. Among patients 23 had active and 19 had inactive disease. IL-1beta, TNF-alpha and IL-8 were determined by enzyme-linked immunosorbent assay ( ELISA), acute phase proteins were measured by nephelometric assay. RESULTS: There was no statistically significant difference between mean IL-1beta levels of patient groups and controls. Serum mean TNF-a levels in active and inactive patients were significantly increased as compared to that in the controls (P < 0.05, P < 0.05, respectively). Serum mean IL-8 levels in active patients was significantly increased as compared to that in the controls and in inactive patients (P < 0.01, P < 0.01, respectively). High serum IL-8 levels correlated well with C-reactive protein and haptoglobulin, but there was no correlation between IL-1beta or TNF-alpha levels and acute phase proteins such as C-reactive protein, alpha-1 acid glycoprotein, alpha-1 antitrypsin and haptoglobulin. CONCLUSIONS: These results suggest that serum IL-8 may reflect clinical activity of the disease and may be helpful for monitoring patients with SpA.     

IL-1 beta induces COX2, MMP-1, -3 and -13, ADAMTS-4, IL-1 beta and IL-6 in human tendon cells.

Overuse injuries and trauma in tendon often involve acute or chronic pain and eventual matrix destruction. Anti-inflammatory drugs have been used as a treatment, however, the cellular and molecular mechanisms of the destructive processes in tendon are not clearly understood. It is thought that an inflammatory event may be involved as an initiating factor. Mediators of the inflammatory response include cytokines released from macrophages and monocytes. Interleukin-1 beta (IL-1 beta) is a candidate proinflammatory cytokine that is active in connective tissues such as bone and cartilage. We hypothesized that tendon cells would express receptors and respond to IL-1 beta in an initial "molecular inflammation" cascade, that is, connective tissue cell expression of cytokines that induce matrix destructive enzymes. This cascade results in expression of matrix metalloproteinases (MMPs) and aggrecanases that may lead to matrix destruction. Normal human tendon cells from six patients were isolated, grown to quiescence and treated with human recombinant IL-1 beta in serum-free medium for 16 h. Total RNA was isolated and mRNA expression assessed by semiquantitative RT-PCR. IL-1 beta (1 nM) induced mRNAs for cyclooxygenase 2 (COX2), MMP-1, -3, -13 and aggrecanase-1 as well as IL-1 beta and IL-6, whereas mRNAs for COX1 and MMP-2 were expressed constitutively. The IL-1 beta-treated tendon cells released prostaglandin E(2) (PGE(2)) in the medium, suggesting that the inducible COX2 catalyzed this synthesis. Induction of PGE(2) was detectable at 10 pM IL-1 beta. IL-1 beta also stimulated MMP-1 and -3 protein secretion. Induction of MMP-1 and -3 was detectable at 10 pM IL-1 beta. Post-injury or after some other inciting events, exogenous IL-1 beta released upon bleeding or as leakage of local capillaries may drive a proinflammatory response at the connective tissue cell level. The resulting induction of COX2, MMP-1 and -3 may underscore a potential for nonlymphocyte-mediated cytokine production of MMPs that causes matrix destruction and a loss of tendon biomechanical properties. Endogenous IL-1 beta might contribute to the process through a positive feedback loop by stimulating expression and accumulation of MMPs in the tendon matrix.     

ARDS和SIRS病人血浆TNF-α、IL-1β、IL-6及IL-10水平的变化

目的:通过检测分析 ARDS 和 SIRS 病人血浆前炎症细胞因子肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)、白介素6(IL-6)和抗炎细胞因子白介素10(IL-10)水平的变化,探讨这些细胞因子在全身炎症反应和急性肺损伤中的作用。方法:选择临床诊断 ARDS 病例22例和 SIRS 8例,以及正常对照10例,收集血浆,采用酶联免疫法(ELISA)检测 TNF-α、IL-1β、IL-6和 IL-10蛋白含量。结果:SIRS 病人血浆 TNF-α、IL-1β、IL-6和 IL-10含量分别为206.1±85.9 pg/ml、313.6±76.7 pg/ml、141.4±41.5 pg/ml 和259.6±54.34 pg/ml,均显著低于ARDS 病人(分别为629.3±187 pg/ml、892.4±209 pg/ml、261.1±71.3 pg/ml 和458.1±111.93 pg/ml);但SIRS 和 ARDS 病人上述细胞因子水平均显著高于正常对照组。结论:TNFα、IL-1β和 IL-6是 SIRS 和 ARDS 演变中的重要炎症细胞因子,抗炎细胞因子 IL-10的过度释放在促进炎症反应向失控发展、急性肺损伤发展成ARDS 中发挥一定作用。     

高渗氯化钠溶液对前列腺素E2、白介素—2和白介素—6的影响

目的：对比观察7．5％高渗氯化钠溶液（HTS）对人类前列腺素E2（PGE2）,IL－2和IL－6的影响，探讨其对人体免疫功能的调节作用及可能机制。方法：随机将40例ASA Ⅰ-Ⅱ级择期手术病人分为两组（每组20例）：A组在麻醉前输入7．5％HTS4ml/kg；B组在麻醉前输入等量的复方氯化钠溶液，随后均以复方氯化钠溶液维持循环稳定，分别于输液前（T1），输液后1．5小时（T2）和输液后24小时（T3）取血测PGE2，IL－2，和IL－6。结果：A组病在T3时PGE2明显降低（P＜0．01），与B组比较，A线IL－2，IL－6有上升趋势，但无统计学意义。结论：高渗氯化钠溶液可以降低血PGE2水平。     

A chimeric form of osteoprotegerin inhibits hypercalcemia and bone resorption induced by IL-1beta, TNF-alpha, PTH, PTHrP, and 1, 25(OH)2D3.

Osteoprotegerin (OPG) is a secreted protein that inhibits osteoclast formation and activity and appears to be a critical regulator of bone mass and metabolism. In the current study, mice were challenged with various cytokines and hormones (interleukin-1beta, tumor necrosis factor-alpha, parathyroid hormone, parathyroid hormone-related protein, and 1alpha,25-dihydroxyvitamin D3) that are known to increase bone resorption and cause hypercalcemia and treated concurrently with either a recombinant chimeric Fc fusion form of human OPG, with enhanced biological activity (cOPG) (2.5 mg/kg/day) or vehicle. Mice receiving these bone-resorbing factors became hypercalcemic by day 3 after commencing treatment and had increased bone resorption as evidenced by elevated osteoclast numbers on day 5. Concurrent cOPG treatment prevented hypercalcemia (p < 0.05) and maintained osteoclast numbers in the normal range (p < 0.001). The demonstration that cOPG can inhibit bone resorption suggests that this molecule may be useful in the treatment of diseases including hyperparathyroidism, humoral hypercalcemia of malignancy, osteoporosis, and inflammatory bone disease, which are characterized, in part, by increases in osteoclastic bone resorption.     

Comparison of IL-8, IL-6 and PGE2 Formation by Visceral (Omental) Adipose Tissue of Obese Caucasian Compared to African-American Women

Background: One of the key consequences of obesity is an enhanced release of cytokines such as IL-8 and IL-6 by adipose tissue. There may be differences in adiposity, inflammatory markers, and medical co-morbidity between morbidly obese African-American (AA) and Caucasian (CA) women. We hypothesized that there are ethnic differences in inflammatory markers and medical co-morbidities. Methods: We compared the mRNA content in omental fat and the release of IL-8, IL-6 and PGE₂ after a 4-hour incubation of explants of adipose tissue in women undergoing bariatric surgery. In addition, medical co-morbidities and fat measurements were examined and compared. Results: Medication usage differed, with CA women being three times more likely to report taking medication for depression compared to AA women (P≤0.001). IL-8 and PGE₂ release over 4 hours by omental fat in vitro was the same in CA and AA women. Similar results were seen with respect to the COX-2 mRNA and IL-8 mRNA values at the start and at the end of the incubation. In CA and AA women, the IL-6 mRNA content in fat immediately after removal from the patients was the same. Conclusions: In morbidly obese women seeking bariatric surgery, there are little ethnic differences between cytokine release by omental adipose tissue explants in vitro, or the mRNA content in omental adipose tissue of IL-6, IL-8 or COX-2. The only noted difference between AA and CA morbidly obese women was the greater use of antidepressants by CA women.     

Increased interleukin-8 (IL-8) expression is related to aseptic loosening of total hip replacement

Aseptic loosening is an increasing problem in total hip replacement (THR). Chronic inflammatory reaction against implant wear particle results in collageno- and osteolysis, leading to loosening of the implant. Cytokines are known to play a major role in this particular inflammatory process [10]. The aim of the present study was to examine interleukin-8 (IL-8) in the synovial-like interface membrane (SLIM) and pseudocapsular tissue of THRs and to compare it to normal knee synovial membrane. Eleven patients suffering from aseptically loosened THRs were included. All the SLIM and pseudocapsular tissue samples were obtained during revision operations. Ten control samples of normal synovium were collected per arthroscopy from the superior recessus of the knee. For immunohistochemical IL-8 detection, polyclonal mouse anti-human immunoglobulin (Ig)G₁ IL-8-primary antibody was used with the alkaline phosphatase anti-alkaline phosphatase (APAAP) method. Results were quantitated using the Vidas image analysis system. The highest count levels (mean ± SEM) were detected in SLIM tissue (386 ± 82 cells/mm²). The difference was statistically significant compared with pseudocapsular tissue (193 ± 36 cells/mm²) and control samples (18 ± 5 cells/mm²). Count levels in control tissue were on average 5% of the SLIM tissues values. The present study determines for the first time the cellular origin of IL-8 in aseptically loosened THRs and also quantitates the IL-8-producing cells in the periprosthetic tissue. The results reveal a high rise in IL-8 concentration in SLIM and in synovial tissues. This finding moves us one step forward in solving the complex network of multiple factors affecting loosening of hip implants. Received: 10 November 1998     

Interleukin-6, procalcitonin and TNF-alpha: markers of peri-prosthetic infection following total joint replacement

This prospective study evaluates the role of new laboratory markers in the diagnosis of deep implant infection in 78 patients (41 men and 37 women) with a revision total knee or hip replacement. The mean age at the time of operation was 64.0 years (19 to 90). Intra-operative cultures showed that 21 patients had a septic and 57 an aseptic total joint replacement. The white blood cell count, the erythrocyte sedimentation rate and levels of C-reactive protein, interleukin-6, procalcitonin and tumour necrosis factor (TNF)-alpha were measured in blood samples before operation. The diagnostic cut-off values were determined by Received Operating Characteristic curve analysis. C-reactive protein (> 3.2 md/dl) and interleukin-6 (> 12 pg/ml) have the highest sensitivity (0.95). Interleukin-6 is less specific than C-reactive protein (0.87 vs 0.96). Combining C-reactive protein and interleukin-6 identifies all patients with deep infection of the implant. Procalcitonin (> 0.3 ng/ml) and TNF-alpha (> 40 ng/ml) are very specific (0.98 vs 0.94) but have a low sensitivity (0.33 vs 0.43). The combination of C-reactive protein and interleukin-6 measurement provide excellent screening tests for infection of a deep implant. A highly specific marker such as procalcitonin and pre-operative aspiration of the joint might be useful in identifying patients with true positive C-reactive protein and/or interleukin-6 levels.