Circulating proinflammatory cytokines (IL-1 beta, TNF-alpha, and IL-6) and IL-1 receptor antagonist (IL-1Ra) in fulminant hepatic failure and acute hepatitis.

Fulminant hepatic failure (FHF) is characterized by massive necroinflammation of the liver tissue and is associated with high mortality. Serum concentrations of IL-1 beta, tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-1 receptor antagonist (IL-1Ra) were measured in 30 patients with FHF and in 23 patients with acute hepatitis (AH) before start of treatment and in 23 healthy controls. Levels of all four molecules were increased significantly in FHF compared with AH, in which values were higher than in the healthy controls. High serum levels of IL-1 beta and a significantly reduced ratio of IL-1Ra to IL-1 beta (IL-1Ra/IL-1 beta) were observed in FHF patients who subsequently died compared with subjects who survived. TNF-alpha and IL-6 concentrations were correlated with levels of human hepatocyte growth factor (hHGF), an index of hepatocyte regeneration. Although serum cytokine levels varied considerably between patients within each group studied, it is suggested that the striking elevation in proinflammatory cytokine levels in FHF may reflect both the insufficiency of hepatitis virus elimination and a failure to control a vicious cytokine cascade leading to overwhelming hepatocyte destruction rather than regeneration. The high cytokine levels observed in these patients and the significantly elevated IL-1Ra/IL-1 beta ratio in FHF patients who survived compared with those who did not suggest the possible therapeutic use of cytokine antagonists for the control of this life-threatening disease.     

Circulating interleukin 10 and interleukin-6 serum levels in rheumatoid arthritis patients treated with methotrexate or gold salts: Preliminary report

In order to evaluate the relationship between serum concentrations of interleukin-10 (IL-10), IL-6, and acute phase proteins in rheumatoid arthritis (RA) patients treated with methotrexate (MTX) or intramuscular gold (IMG) we determined IL-10, IL-6, C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP) and alpha-1-antichymotrypsin (ACT) in the sera of 35 RA patients. IL-10 and IL-6 levels were evaluated using an enzyme-linked immunoassay (ELISA). AGP and ACT level were measured using rocket immunoelectrophoresis. IL-10 serum level was not increased in RA patients as compared to controls (58.7 ± 18.1 pg/ml vs. 57.2 ± 11.9 pg/ml). IL-6 level was significantly elevated (91.6 ± 46.9 pg/ml vs. 45 ± 19 pg/ml, p < 0.05). CRP was significantly increased as compared to healthy controls (35 ± 19 mg/l vs. 3 ± 2 mg/l, p < 0.05). Patients treated with MTX or IMG presented an increased level of IL-10 and decreased amounts of IL-6, as compared to those treated with NSAID only. However, only changes between patients treated with IMG and NSAID were found to be statistically significant. A good negative correlation between IL-10 and IL-6 serum level was found (r = –0.75, p < 0.05). A positive significant correlation between IL-6 serum level and CRP (r = 0.62, p < 0.05), AGP (r = 0.78, p < 0.05) and ACT (r = 0.45, p < 0.05) was established. On the other hand, a negative correlation between IL-10 and serum level of CRP (r = –0.76, p < 0.05), AGP (r = –0.64, p < 0.05) and ACT (r = –0.38, p < 0.05) was also observed. Moreover, these relationships were maintained when patients treated with MTX, IMG, or NSAID were analyzed independently. According to the data thus far obtained, it seems that IL-10 decreases IL-6 production, and thereby indirectly affects the acute phase response, decreasing CRP, AGP, and ACT concentration in RA patients.Abbreviations ACT -1-antichymotrypsin - AGP ₁-acid glycoprotein - APP acute phase protein - CRP C-reactive protein - CSF colony stimulating factor - IFN interferon - IL interleukin - IMG intramuscular gold - MTX methotrexate - NSAID non-steroidal anti-inflammatory drug - RA rheumatoid arthritis     

病毒性肝炎患者血清IL-6和T细胞亚群的关系

采用ＭＴＴ比色法和抗体致敏的红细胞花环试验（间接法）　检测了９１例病毒性肝炎患者血清ＩＬ－６和Ｔ细胞亚群。　结果显示，病毒性肝炎患者血清ＩＬ－６活性均明显高于正常对照组（Ｐ＜０．０１），以重型肝炎为最高；且与肝细胞损害程度呈正比（Ｐ＜０．０１）；ＣＤ４~＋细胞、ＣＤ４＋／ＣＤ８~＋均明显降低，与血清ＩＬ－６呈负相关；ＣＯ８~＋细胞明显增高，与血清ＩＬ－６呈正相关（Ｐ＜０．０１）。表明，血清ＩＬ－６与机体细胞免疫功能密切相关，二者互为因果，共同参与病毒性肝炎的免疫病理损害，可作为判断病情和预后及免疫调节治疗的监测指标。     

血清中IL-6和IL-10变化与慢性乙肝急性发作导致肝衰竭的关系

目的通过分析急性发作慢性乙型肝炎（慢性乙肝）患者体内IL-6、IL-12、γ干扰素和IL-10的变化,探讨急性发作及病情严重程度与细胞因子变化的关系。方法对154例急性发作及免疫耐受慢性乙肝患者采用ELISA法检测IL-6、IL-12、γ干扰素和IL-10的水平,同时检测肝功能、HBV DNA定量等。结果处于急性发作的患者年龄较大,HBV DNA定量较低,促炎症因子和抗炎症因子的水平均高于处于免疫耐受的患者;重型肝炎组IL-6的水平（179.80±134.96）pg/ml高于非重型肝炎组（108.80±113.23）pg/ml（P〈0.05）,而IL-10的水平（12.80±4.96）pg/ml低于非重型肝炎组（20.33±7.35）pg/ml（P〈0.05）。结论慢性乙肝急性发作可能与炎症因子的激活相关,IL-6有促进肝损伤作用,而IL-10可能在避免过强免疫损伤中起重要作用。     

Serum interleukin-10 in ICU patients with severe acute central nervous system injuries

Rationale:IL-10, the main anti-inflammatory cytokine, may play a pivotal role in cerebral inflammation implicated in the development of brain edema and secondary brain damage after injury. Aim of the study:1) Determining absolute IL-10 serum level and its pattern in critically ill patients with traumatic and non-traumatic acute brain injury. 2) Assessment of prognostic value of serum IL-10 in those patients. Materials and methods:Serum IL-10 levels in 46 adults (multi-profile ICU, teaching hospital) with traumatic brain injury (TBI, N = 18), nontraumatic intracranial hemorrhage (SAH, N = 11) and polytrauma with concomitant brain injury (POL, N = 17) were measured using ELISA. Relationship of IL-10 and initial diagnosis, clinical state, outcome and risk of infection development was evaluated. Results:IL-10 was detectable in the serum of all but one patient on ICU admission (56.6 ± 91.9 pg/ml; mean ± SD). No statistically significant differences in IL-10 between TBI, SAH and POL groups as well as between survivors and non-survivors on any day were found. No correlation between IL-10 and GCS or SAPS II was seen. Significant fall in serum IL-10 during the first 4 days of injury in patients of all subgroups was observed. Patients with initial serum IL-10 below 77pg/ml were at significantly higher risk of development of any infection within the first week of injury. Conclusions:After acute brain injury, serum IL-10 in adults is detectable independent of CNS lesion type. Its systemic release is strongly individualized. Serum IL-10 on ICU admission may have some prognostic value to predict development of infection in patients with CNS lesions.Received 26 June 2003; returned for revision 2 December 2003; accepted by A. Falus 26 February 2004     

Interrelationships between interleukin (IL)-1, IL-6 and IL-8 in synovial fluid of various arthropathies

High levels of many cytokines, including interleukin (IL)-1, IL-6 and IL-8, were found in various arthropathies suggesting that they play a role in the pathogenesis of disease, although their relationship with the type and activity of disease is still not clear. The synovial fluid (SF) of 24 patients with rheumatoid arthritis (RA), 19 with psoriatic arthritis (PA) and 33 with osteoarthritis (OA) was analyzed for IL-1, IL-6 and IL-8. The highest concentration of the three cytokines was found in the SF of RA. IL- detectable levels (>-20 pg/ml) were observed in 8/24 (33.3%) patients with RA, in one patient with PA but in no patient with OA.IL-6 (mean±SD) (1610.37±1781.65 pg/ml) was higher in RA than in PA (672.47±867.40 pg/ml,p=0.043) and OA (89.45±120.52 pg/ml,p=0.0001). IL-8 (1042.72±698.64 pg/ml) was higher in RA than in PA (660.36±625.11 pg/ml,p=0.03) and OA (89.9±45.88 pg/ml,p=0.0001). A correlation between IL-1, IL-6 and IL-8 was found in RA. In all patients a correlation between IL-6 and IL-8 levels was found; moreover, these two cytokines were associated with SF indices of inflammation, such as white blood cells (WBC) count and total protein (TP) concentration.Out findings suggest that these interrelationships play a role in the evolution of more severe erosive arthropathy such as RA.     

Vitamin B12 and folic acid deficiency in chronic pancreatitis: a relevant disorder?

Summary Vitamin B12 malabsorption was reported earlier to occur in patients with exocrine pancreatic insufficiency, and pancreatic extracts were shown to improve the absorption of vitamin B12. We investigated serum levels of vitamin B12 and serum folate in patients with chronic pancreatitis and different degrees of pancreatic insufficiency.137 patients (84 males, 53 females, age 34–72 years) with chronic pancreatitis (C.P.) were included in the study. 123 of 137 (89.8%) patients had a pathologic pancreatic function test result, classified into mild (n=24), moderate (n=61) or severe (n=38) insufficiency. The normal range of serum vitamin B12 and folic acid was established in 58 healthy controls and was found to be 190–1020 pg/ml for serum vitamin B12 and 2.4–16.1 ng/ml for folic acid. 7 patients (5.7%) with C.P. had vitamin B12 serum levels below 190 pg/ml; 4 of these had severe and 3 had mild or moderate exocrine pancreatic insufficiency. However there was no overall correlation between the degree of pancreatic insufficiency and vitamin B12 values. Serum levels of Vitamin B12 were 512±48 pg/ml in mild, 493±52 pg/ml in moderate and 428±45 pg/ml in severe exocrine insufficiency. Serum folic acid below 2.4 ng/ml were present in 5 patients (3.6%). Folic acid serum levels were 8.34±0.76 ng/ml in mild, 6.34±0.52 ng/ml in moderate and 7.45±0.53 ng/ml in severe exocrine insufficiency. We conclude that vitamin B12 deficiency is a rare finding in chronic pancreatitis and does not strictly depend on the degree of exocrine pancreatic insufficiency. In clinical practice enzyme supplementation in patients with severe pancreatic insufficiency is obviously sufficient for normal vitamin B12 absorption. Folic acid deficiency is also unfrequently found in chronic pancreatitis.     

Elevated serum BAFF levels in patients with autoimmune hepatitis

Serum cytokines are thought to be involved in autoimmune hepatitis (AIH) pathogenesis via immune dysregulation. B-cell activating factor belonging to the tumor necrosis factor family (BAFF) is a member of the tumor necrosis factor (TNF) superfamily and is known for its role in the survival and maturation of B cells. The aim of the study was to evaluate the serum levels of BAFF in patients with AIH and determine its relation to the clinical features of AIH. We examined serum BAFF levels in 55 patients with AIH, 14 patients with acute hepatitis (AH), 33 patients with chronic hepatitis C, and 33 healthy subjects by enzyme-linked immunosorbent assay. Liver function tests, quantitative immunoglobulin, and antinuclear antibody levels were also assayed in AIH patients. Serum BAFF levels were elevated in AIH patients compared with healthy subjects (AIH: 2.07+/-1.21 pg/ml, control: 0.77+/-0.22 pg/ml). Similarly, serum BAFF levels were significantly higher in AIH patients compared with AH or chronic hepatitis C patients. There was a positive correlation between BAFF and aspartate aminotransferase (r=0.513, p<0.0001), alanine aminotransferase (r=0.435, p<0.0001), total bilirubin (r=0.419, p<0.01), and soluble CD30 (r=0.579, p<0.0001) in AIH patients. However, there was no correlation between BAFF and levels of gammaglobulins or titer of antinuclear antibodies. Corticosteroid treatment resulted in marked reduction in serum BAFF levels in AIH patients. These results suggest that BAFF contributes to liver injury and disease development in AIH patients.     

The levels of IL-1beta, IL-4 and IL-6 in the serum and the liver tissue of chronic HCV-infected patients.

The pro-inflammatory interleukines play a major role in the progress of chronic hepatitis C. Among the patients with chronic hepatitis C virus (HCV) infection, the morphology of the liver was assessed and the levels of serum and liver-tissue IL-1beta, IL-4 and IL-6 were determined. The levels of the cytokines were related to the liver-tissue changes. RNA-HCV was measured by the RT-PCR method. Cytokine levels of the serum and liver tissue were measured by the Quantikine High Sensitivity test. The levels of serum IL-1beta, IL-4 and IL-6 (0.221, 0.104 and 1.393 pg/ml) in all HCV patients were higher in comparison with healthy adults (0.188, 0.025 and 0.600 pg/ml). The levels of liver tissue IL-1beta, IL-4 and IL-6 (4291.3, p<0.05; 1624.6, p<0.05; 1158.7 pg/g protein) in all HCV patients were higher compared with patients with liver cirrhosis without HBV or HCV infection (2319.9, 553.6 and 756.2 pg/g protein). Patients with HCV infection demonstrated a significant correlation between serum and liver-tissue levels of IL-1beta (Pearson: 0.61, p<0.05) and IL-4 (Pearson: 0.51). The level of serum IL-6 in patients with moderate chronic active hepatitis was higher when compared with patients with mild chronic persistent hepatitis. Among the patients with mild chronic persistent hepatitis, the levels of liver-tissue IL-6 were higher compared with those with moderate chronic active hepatitis. There was no correlation between histology changes and the levels of serum and liver-tissue IL-1beta and IL-4.     

Clinical significance of serum IL-18 determination in rheumatoid arthritis

Interleukin (IL)-18 is a novel cytokine expressing at inflammatory lesion. In this study, to evaluate the clinical significance of IL-18 determination, we have examined serum IL-18, inflammation markers, sFas, and sFas-ligand concentrations in patients with rheumatoid arthritis(RA). Serum was obtained from 56 RA patients aged 35-74 years, 16 osteoarthritis (OA) patients aged 36-78 years and 178 healthy subjects aged 20-72 years and IL-18 was measured by ELISA. Serum IL-18 concentrations in RA (240.1 +/- 15.6 pg/ml, mean +/- SE) were significantly higher than OA (151.8 +/- 12.7 pg/ml, p < 0.005) and healthy controls(141.5 +/- 26.1 pg/ml, p < 0.001). Serum IL-18 levels were significantly increased in II to IV stages of RA (stage II; 218.6 +/- 31.2 pg/ml, stage III; 258.7 +/- 38.4 pg/ml, stage IV; 231.6 +/- 13.1 pg/ml) than those in OA. Furthermore, a positive correlation was observed between serum IL-18 concentration and serum Fas level in patients with RA (r = 0.472), whereas there was no significant correlation between serum IL-18 and sFas-ligand or other inflammatory markers (CRP, RF, CA-RF, IL-6, and IL-8). The present study showed that serum IL-18 level increased in RA, but it is unknown how IL-18 is involved in the pathogenesis of RA. Further study will be necessary to clarify the role of IL-18 in RA.     

用ROC曲线评价IL-6早期诊断重症急性胰腺炎的临床价值

目的:用ROC曲线评价白介素-6(interleukin-6,IL-6)早期诊断重症急性胰腺炎的临床价值.方法:收集96例急性腹痛患者的肝素锂抗凝血浆各1ml置-20℃.根据其后的临床诊断资料将病人分为三组:非胰腺炎急腹症50例,重症急性胰腺炎17例,轻症急性胰腺炎29例.相同方法收集50份各项指标正常的体检标本.用DGGR底物连续监测法测定脂肪酶(lipase,LPS),用DPC IMMULITE化学发光法测定IL-6,用ROC曲线评价LPS和IL-6的早期诊断重症急性胰腺炎的临床价值.结果:用LPS鉴别诊断非胰腺炎性急腹症和急性胰腺炎时,cutoff值取94 U/L,灵敏度(Se)=0.98,特异性(Sp)=0.98,AUC=0.998,LPS能较好的鉴别诊断非胰腺炎性急腹症和急性胰腺炎.用IL-6鉴别诊断重症急性胰腺炎和轻症急性胰腺炎时,cutoff值取11pg/ml,Se=1.00,Sp = 0.86,AUC=0.925,IL-6能较好的鉴别诊断重症急性胰腺炎和轻症急性胰腺炎.结论:DGGR底物连续监测法测定LPS和DPC IMMULITE化学发光法测定IL-6,不仅提高了灵敏度和特异性,而且加快了检测速度,确保了LPS和IL-6的准确及时报告,促进了临床的广泛应用.LPS和IL-6结合使用对早期诊断重症急性胰腺炎有较高的临床价值.     

Membrane staining for hepatitis B surface antigen on hepatocytes: a sensitive and specific marker of active viral replication in hepatitis B.

AIMS--To test the hypothesis that membranous staining of hepatitis B surface antigen (HBsAg) on the hepatocyte is a marker of active viral replication in chronic hepatitis B virus (HBV) infection. METHODS--Intrahepatic expression of HBsAg and hepatitis B core antigen (HBcAg) was studied by indirect immunofluorescence on frozen sections of liver specimens from 75 patients with chronic hepatitis B, and the results were correlated with serum levels of HBV-DNA assayed by spot hybridisation. RESULTS--Hepatocyte HBcAg was detected in all of 20 patients with serum levels of HBV-DNA > 1000 pg/ml, 18 (75%) of 24 patients with levels of HBV-DNA < or = 1000 pg/ml, and two (6.5%) of 31 patients without detectable serum HBV-DNA. The concordance between hepatocyte HBcAg and serum HBV-DNA was 89.3% (67/75). There were six patients (8%) who had detectable serum HBV-DNA but without hepatocyte HBcAg, and two patients (2.7%) who had detectable hepatocyte HBcAg but without serum HBV-DNA. Membranous staining of HBsAg associated with variable degrees of cytoplasmic HBsAg was found in all but one of 44 patients with serum HBV-DNA, irrespective of the levels, but in none of the 31 patients without serum HBV-DNA. Of the latter, HBsAg was distributed solely in the cytoplasm. In addition, there is an inverse correlation between serum levels of HBV-DNA and the degrees of cytoplasmic staining of HBsAg. The concordance between membranous staining fo HBsAg and serum HBV-DNA was 98.7% (74/75), significantly higher than that between hepatocyte HBcAG and serum HBV-DNA. CONCLUSIONS--Membranous staining of HBsAg on the hepatocyte correlated excellently with serum HBV-DNA and thus can be recognised as a sensitive and specific marker of active hepatitis B virus replication.     

Significantly Higher Cytokine and Chemokine Levels in Patients with Japanese Spotted Fever than in Those with Tsutsugamushi Disease

Tetracyclines are administered to cure Japanese spotted fever (JSF) and tsutsugamushi disease (TD). It is generally said that the clinical course of JSF is worse than that of TD despite antibiotic treatment. The precise mechanism underlying the more severe clinical course of JSF is not fully understood. We therefore examined whether the differential cytokine profile between these two infectious diseases contributes to the difference in clinical severity. The serum concentrations of various cytokines (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], and gamma interferon [IFN-γ]) and chemokines (IL-8, interferon-inducible protein 10 [IP-10], monocyte chemoattractant protein 1 [MCP-1], macrophage inflammatory protein 1α [MIP-1α], MIP-1β, and eotaxin) were measured in 32 TD and 21 JSF patients. The results showed that serum levels of TNF-α in the acute phases of TD and JSF were significantly increased, with a higher concentration of TNF-α in patients with JSF (mean, 39.9 pg/ml) than in those with TD (mean, 13.8 pg/ml). Comparatively higher levels of other cytokines and chemokines (IL-6, IFN-γ, IL-8, IP-10, MCP-1, MIP-1α, and MIP-1β) were also observed in the acute phase of JSF. The clinical severity score (3.67 ± 1.71) of JSF patients was higher than that of TD patients (1.47 ± 0.77). Our findings revealed that the cytokine and chemokine levels in the acute phase of JSF were significantly higher than those in the acute phase of TD. The differential cytokine levels may be related to the difference in clinical severity between JSF and TD.     

成人麻疹并急性肝损害患者血清IL-33 高表达的临床意义

目的:探讨麻疹并急性肝损害患者血清IL-33 的水平变化及临床意义。方法:选取成人麻疹并肝损害60 例为研究对象,无肝损害28 例为对照,同时纳入查体中心20 例健康人为健康对照。采用酶联免疫吸附测定法( ELISA 法) 测定血清IL-33 的水平,于第0、7、14 天动态观察肝损害组血清IL-33 变化,并分析血清IL-33 水平与临床生化及炎症指标的相关性。将60 例肝损害患者按照随机数字法分为保肝组和无保肝组,各30 例,对比第7 和14 天两组患者间血清IL-33 变化。结果:麻疹并肝损害、麻疹无肝损害患者血清IL-33 水平分别为(205.20±25.74) pg/ ml、(168.70±18.14) pg/ ml,均显著高于健康对照[(132.17±12.41) pg/ ml,P<0.05],以肝损害组显著;第7 天,无保肝组血清IL-33 表达显著高于保肝组。第14 天,保肝和无保肝两组间血清IL-33 表达差异无统计学意义(P>0.05);随时间延长,肝损害组患者血清IL-33 呈下降趋势,于治疗第14天与健康对照组间差异无统计学意义(P>0.05);血清IL-33 水平与肝损害的程度一致。相关分析提示IL-33 与ALT、GGT、IL-6 呈正相关(r =0.392 1、0.503 9、0.724 9,P<0.001)。结论:血清IL-33 在麻疹肝损害中呈高水平表达,IL-33 可能参与麻疹病毒诱发的急性肝损害的发生、发展及转归。     

Twelve potential fibrosis markers to differentiate mild liver fibrosis from cirrhosis in patients infected with chronic hepatitis C genotype 1

Information about the stage of liver fibrosis is important for managing patients with chronic hepatitis C (CHC). The aim of this study was to evaluate 12 plasma markers for differentiating no/mild liver fibrosis from cirrhosis among patients with CHC genotype 1. Transient elastography was used to assess the stage of fibrosis for the patients included in the study. Forty patients were included (21 cirrhotic). Plasma levels of tumor necrosis factor-α (TNF-α), interleukin 8 (IL-8), interferon-γ inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), soluble urokinase-type plasminogen activator (suPAR), monokine induced by γ-interferon (MIG), human hepatocyte growth factor (HGF), insulin, interleukin 6 (IL-6), interleukin 1-β (IL-1β), leptin, and nerve growth factor (NGF) were analyzed. Concentrations of TNF-α (median 15.0 vs. 25.1 pg/ml, area under the receiver operating characteristic curve [AUC] 0.91), IL-8 (48.7 vs. 103.3 pg/ml, AUC 0.85), IP-10 (176 vs. 566 pg/ml, AUC 0.83), MCP-1 (449 vs. 735 pg/ml, AUC 0.78), suPAR (3.5 vs. 5.2 ng/ml, AUC 0.78), MIG (100 vs. 152 pg/ml, AUC 0.75), and HGF (3.69 vs. 5.58 ng/ml, AUC 0.71) were significantly higher in patients with cirrhosis. In conclusion, several of the investigated markers showed promise for differentiating cirrhosis from no/mild fibrosis among patients with CHC genotype 1.     

Which is more important after total knee arthroplasty: Local inflammatory response or systemic inflammatory response?

We aimed to determine the relationship between functional recovery after knee arthroplasty and systemic and local inflammatory responses. A prospective, clinical study of thirty patients who had osteoarthritis was conducted. After the total knee arthroplasty (TKA), intraarticular IL-6 levels, serum IL-6 levels and serum CRP levels were measured. The primary outcome measures for functional recovery after TKA were the the Knee Society Score (KSS) and Western Ontario and McMaster Universities Index (WOMAC). All patients were examined preoperatively and at 4, 8 and 24 weeks postoperatively. The mean postoperative intraarticular IL-6 level was 218355.1 pg/ml, the mean postoperative serum CRP level was 109.9 mg/L and the mean postoperative serum IL-6 level was 219.0 pg/ml. Preoperative and 4-, 8- and 24-week postoperative KSS and WOMAC scores were evaluated. Significant correlations were found between intraarticular IL-6 concentrations and KSS and WOMAC scores at the first month according to the Pearson correlation test, but no correlations were found between serum IL-6 and CRP levels and KSS and WOMAC scores. The local inflammatory response is more important than the systemic response for early postoperative functional recovery. After TKA, control of local inflammation is much more important than control of systemic inflammation.     

Thrombolytic therapy with urokinase reduces increased circulating endothelial adhesion molecules in acute myocardial infarction

The aim was to investigate circulating E-selectin and Intercellular Adhesion Molecule-1 (ICAM-1) in acute myocardial infarction. Our study was carried out in 80 patients, 40 hospitalized for acute myocardial infarction (AMI), 20 suffering from chronic stable angina and 20 healthy control subjects. Samples of venous blood were taken from all patients at the moment of hospitalization and after 2, 4, 6, 8, 10, 12 and 24 hours from the thrombolytic treatment (AMI+urokinase) or conventional therapy (AMI+nitroglycerin), for the dosage of creatinine kinase (CK) and adhesion molecules. The CK was determined by means of a Hitachi 901 automatic analyser using an enzymatic method (reagents Boheringer-Biochemia, Germany). Soluble E-selectin (sE-selectin) and soluble ICAM-1 (sICAM-1) were measured in the serum using a specific immunoassay (British Biotechnology Products). The serum levels of Tumor Necrosis Factor (TNF-) were evaluated using an immunoenzymatic assay to quantitate the serum levels of the cytokine British Biotechnology Products). Patients with acute myocardial infarction (AMI) had increased serum levels of soluble E-selectin (sE-selectin; AMI+urokinase= 312±20 ng/ml; AMI+nitroglycerin=334±15 ng/ml) and soluble ICAM-1 (sICAM-1; AMI+urokinase= 629±30ng/ml; AMI+nitroglycerin=655±25 ng/ml) compared to both patients with chronic angina (sE-selectin =67±10 ng/ml; sICAM-1=230±20 ng/ml) and healthy control subjects (sE-selectin=53±15 ng/ml; sICAM-1 200±16 ng/ml). Furthermore patients with acute myocardial infarction also had increased serum levels of Tumor Necrosis Factor (TNF-=309±10 pg/ml; control subjects=13±5 pg/ml). Thrombolytic therapy with urokinase (1,000,000 IU as an intravenous bolus for 5 minutes, followed by an infusion of an additional 1,000,000 IU for the following two hours) succeeded in producing reperfusion and reduced the serum levels of sE-selectin (52±13 ng/ml) and sICAM-1 (202±31 ng/ml). In contrast patients not eligible for thrombolytic therapy and therefore treated with conventional therapy (a continuous i.v. infusion of nitroglycerin at the dose of 50 mg/die) did not show any significant reduction in both sE-selectin and sICAM-1 throughout the study. Our results confirm previous experimental data and indicate that adhesion mechanisms supporting leukocyte-endothelium interaction may also be operative in human acute myocardial infarction.accepted by I. Ahnfelt-Rønne     

Role of Th1 and Th2 Cytokines in Immune Response to Uncomplicated Plasmodium falciparum Malaria

The relative balance between Th1 and Th2 cytokines appears crucial, since the role of cytokines has been evaluated in several studies by comparison of clinically heterogeneous groups of patients. The aim of this study is to determine the role of proinflammatory Th1 cytokines, interleukin-12 (IL-12) and gamma interferon (IFN-γ), and anti-inflammatory Th2 cytokines, IL-4 and IL-10, in a homogeneous group of patients with uncomplicated Plasmodium falciparum malaria. Levels of IL-12, IFN-γ, Il-4, and IL-10 in serum for 20 adult patients and 15 healthy control subjects were determined by an immunoenzymatic assay. Serum levels of Th1 cytokines, IL-12 (8.6 ± 2.8 pg/ml; controls, 3.2 ± 0.7 pg/ml) and IFN-γ (39.2 ± 67.6 pg/ml; controls, 8.4 ± 6.3 pg/ml), were significantly increased at admission; 3 days later, levels of IL-12 in serum remained significantly high (8.8 ± 2.6 pg/ml), whereas IFN-γ levels returned to control values. The anti-inflammatory response of Th2 cytokines (IL-10 and IL-4) was distinct. Levels of IL-10 in serum were not significantly increased at day 0 and day 3 (306.6 ± 200.4 pg/ml and 56.6 ± 38.4 pg/ml, respectively; controls, 17.4 ± 9.0 pg/ml). In contrast, levels of IL-4 in serum were not increased on admission (3.4 ± 1.2 pg/ml; controls, 2.4 ± 0.8 pg/ml), but at day 3 a moderate and significant increase of IL-4 levels was observed (4.5 ± 1.7 pg/ml). In conclusion, the increase of Th1 cytokine IL-12 and IFN-γ levels during the acute phase of uncomplicated P. falciparum malaria may reflect an early and effective immune response regulated by proinflammatory Th1 cytokines, and in particular IFN-γ may play a role in limiting progression from uncomplicated malaria to severe and life-threatening complications.     

Determination of serum interleukin-6 concentration by an enzyme-linked immunosorbent assay in patients with paraproteinemia]

A sensitive enzyme-linked immunosorbent assay of human interleukin-6 (IL-6) was developed to measure the serum IL-6 by Fujirebio INC. Its sensitivity was 3 pg/ml and its analytical range was from 3 to 200 pg/ml. Its precision, reproducibility, and sensitivity were quite satisfactory. The serum IL-6 levels in 200 normal individuals were less than 3 pg/ml. Serum IL-6 concentration in patients with malignant and benign monoclonal gammopathy (BMG) was determined by an ELISA. Serum IL-6 concentration in patients with Bence Jones protein (BJP) type multiple myeloma (MM) (n = 12) was 12.3 +/- 12.7 (mean +/- SD) pg/ml, BJP and IgG type MM (n = 4) 11.5 +/- 5.8 pg/ml, IgM type MM (n = 11) 11.1 +/- 17.5 pg/ml and IgA type MM (n = 4) 4.0 +/- 1.4 pg/ml. They were significantly higher in BJP, BJP and IgG, and IgM types than in normal individuals. The cases with the serum IL-6 of more than 10 pg/ml were move frequent in MM (32.8%) than in BMG (16.3%). The correlation between the serum IL-6 and C-reactive protein (CRP) was r = 0.563 in patients with MM (n = 61) and r = 0.498 in BMG (n = 43). Besides, during the clinical course of a patient with IgG-lambda and BJP-lambda type MM, serum IL-6 concentration responded more sharply than CRP and WBC on candida infection. The measurement of serum IL-6 therefore, seemed not useful for differential diagnosis of monoclonal gammopathies, but it seemed useful as an acute phase protein as well as CRP.     

Circulating antiinflammatory cytokine IL-10 in patients with inflammatory bowel disease (IBD).

IBD is characterized by increased serum concentrations of different cytokines. IL-10 inhibits the production of proinflammatory cytokines such as IL-1, tumour necrosis factor-alpha (TNF-a), interferon-gamma (IFN-gamma) and IL-6 through inhibitory action on Th1 cells and macrophages, and it is thought to be a suppressor type cytokine. In the present study we determined serum concentrations of IL-10 in patients with ulcerative colitis (UC) and Crohn's disease (CD). We measured human IL-10 by our own newly established ELISA system using PharMingen antibodies. Serum antibodies were assessed in 44 patients with UC, 40 patients with CD, and in 30 healthy controls. Human IL-10 serum levels were significantly increased in patients with active UC (144 +/- 34 pg/ml (mean +/- s.e.m.), P < 0.001) and in active CD (132 +/- 32 pg/ml, P < 0.001) compared with healthy controls (44 +/- 9.5 pg/ml). Only patients with active CD and active UC presented with significantly increased IL-10 serum levels, while patients with inactive disease did not show any significant increase. There was no statistically significant difference between IL-10 serum levels in patients with CD or UC. Compared with clinical disease activity indices there was a significant correlation between IL-10 serum concentration and CDAI in patients with CD (r = 0.45, P < 0.01) and CAI in UC patients (r = 0.39, P < 0.05). Comparing IL-10 serum levels with serum concentrations of other proinflammatory cytokines there was a significant correlation to serum levels of sIL-2R (r = 0.417, P < 0.05) and IL-6 (r = 0.387, P < 0.05) in patients with CD. Serum cytokine levels in patients with UC did not show any significant correlation to IL-10 serum concentration. IL-10 is elevated in serum of patients with active CD and UC, suggesting that IL-10 acts as a naturally occurring damper in the acute inflammatory process of IBD.