Soluble interleukin-6 receptor in rheumatoid arthritis

Abstract

To investigate the pathophysiologic role of soluble interleukin-6 receptor (sIL-6R) in patients with rheumatoid arthritis (RA), serum sIL-6R levels were measured in 15 RA patients and 15 healthy control subjects using a sandwich enzyme-linked immunosorbent assay. Correlation analysis was performed between sIL-6R levels and clinical variables such as joint score, Lansbury’s index, C-reactive protein and platelet counts. Levels of sIL-6R and IL-6 were also measured in paired samples of serum and synovial fluid obtained at the same time from nine RA patients. Serum sIL-6R levels in RA patients (153.9±56.9 ng/ml) were significantly higher than those of control subjects (115.1±19.1 ng/ml; P<0.05). However, sIL-6R levels did not correlate with any clinical characteristic of RA. sIL-6R was detectable in synovial fluid, but was invariably lower than in serum, in contrast to IL-6 (i.e. much higher in synovial fluid). It correlated neither with total cell nor neutrophil number in synovial fluid. Serum C-reactive protein levels were significantly correlated with IL-6 in synovial fluid, but not with sIL-6R in synovial fluid. These results indicate that serum sIL-6R levels are increased in RA patients. High levels of serum sIL-6R did not seem to be derived from the site of local inflammation. The readily detectable sIL-6R in synovial fluid may co-operate with IL-6 in the pathogenesis of synovitis in RA.     

Soluble interleukin-6 receptor in rheumatoid arthritis

To investigate the pathophysiologic role of soluble interleukin-6 receptor (sIL-6R) in patients with rheumatoid arthritis (RA), serum sIL-6R levels were measured in 15 RA patients and 15 healthy control subjects using a sandwich enzyme-linked immunosorbent assay. Correlation analysis was performed between sIL-6R levels and clinical variables such as joint score, Lansbury’s index, C-reactive protein and platelet counts. Levels of sIL-6R and IL-6 were also measured in paired samples of serum and synovial fluid obtained at the same time from nine RA patients. Serum sIL-6R levels in RA patients (153.9±56.9 ng/ml) were significantly higher than those of control subjects (115.1±19.1 ng/ml;P<0.05). However, sIL-6R levels did not correlate with any clinical characteristic of RA. sIL-6R was detectable in synovial fluid, but was invariably lower than in serum, in contrast to IL-6 (i.e. much higher in synovial fluid). It correlated neither with total cell nor neutrophil number in synovial fluid. Serum C-reactive protein levels were significantly correlated with IL-6 in synovial fluid, but not with sIL-6R in synovial fluid. These results indicate that serum sIL-6R levels are increased in RA patients. High levels of serum sIL-6R did not seem to be derived from the site of local inflammation. The readily detectable sIL-6R in synovial fluid may co-operate with IL-6 in the pathogenesis of synovitis in RA.     

Lack of an association of urinary albumin excretion with interleukin-6 or C-reactive protein in patients with type 2 diabetes

The reason for the elevation of fibrinogen concentration in diabetic patients with nephropathy is not known so far. In order to elucidate the mechanism of such an increase in fibrinogen levels, we investigated haemorheological and inflammatory markers in type 2 diabetic patients in a cross-sectional design. Thirty-two non-smoking type 2 diabetic patients (13 women, 19 men; body mass index 29.1±5.4 kg/m², age 62.8±12.1 years) were investigated. Patietns with C-reactive protein levels > 1.5 mg/dl were excluded from the study. Concentration of fibrinogen was measured by immunonephelometry, C-reactive protein by immunoturbidimetry, and interleukin-6 (IL-6) by an enzyme-linked immunosorbent assay, and viscosity of plasma and of whole blood was determined by rotation viscosimetry. Concentrations of inflammatory parameters were well correlated with each other (p<0.05 for all correlations): IL-6 with C-reactive protein (r=0.48), and C-reactive protein with fibrinogen (r=0.41). While no associations were found with concentrations of C-reactive protein or IL-6, urinary albumin excretion was correlated with erythrocyte sedimentation rate (r=0.47) and with fibrinogen concentration (r=0.39; p<0.05). In patients with type 2 diabetes mellitus, urinary albumin excretion was not associated with concentrations of IL-6 or C-reactive protein. These results suggest an IL-6-independent mechanism for increased fibrinogen levels and erythrocyte sedimentation rate in type 2 diabetic patients with increased urinary albumin excretion. Received: February 2000 / Accepted in revised form: October 2001     

The link between interleukin-6, anti-cyclic citrullinated peptide and highly sensitive C-reactive protein in type 2 diabetes: age-effect study

Anti-cyclic citrullinated peptide (ACCP) autoantibodies are likely to be involved in the development of rheumatoid arthritis in at least 70 % of the patients. These autoantibodies are associated with type 1 diabetes and may predict the development of rheumatoid arthritis in later life. This study aimed to examine the association between interleukin-6 (IL-6), a proinflammatory cytokine, highly sensitive C-reactive protein (hsCRP), and ACCP autoantibodies in type 2 diabetes (T2D) patients without past or current history of arthropathy taking in consideration the age-effect factor. A total number of 70 T2D patients and 60 healthy subjects were recruited from the center of diabetes in Erbil, Iraq. The patients were grouped into two: group I (age 35–45 years): group IA, healthy subjects and group IB, diabetic patients; group II (age ≥60 years): group IIA, healthy subjects and group IIB, diabetic patients. Fasting serum glucose, HbA_1c%, lipid profile, IL-6, hsCRP, and ACCP autoantibodies were determined. Significant alterations in lipid profile were observed in group IIB compared with group IB. Patients of group IIB have significant high serum IL-6 (458.3 ± 43.04 pg/ml), hsCRP (5.576 ± 0.643 mg/L), and ACCP autoantibodies (74.31 ± 8 U/ml) than corresponding group IB: IL-6 (381.4 ± 22.6 pg/ml), hsCRP (4.92 ± 0.343 mg/L), and ACCP (49.43 ± 7.09 U/ml). Significant positive correlation (r = 0.445) between serum IL-6 and ACCP autoantibodies was observed only in group IB. It concludes that proinflammatory markers and autoantibodies that related to arthritis are increased in old diabetic patients compared with younger age, and IL-6 correlated with ACCP autoantibodies in younger patients which indicated age effect.

     

川崎病患儿血清可溶性白细胞介素-2受体和白细胞介素-6的变化及意义

目的探讨血清可溶性白细胞介素-2受体(sIL-2R)和白细胞介素-6(IL-6)水平在川崎病(K D)患儿中的变化,及其在发病中的作用。方法采用酶联免疫吸附试验(ELISA)双抗夹心法测定血清sIL-2R和IL-6水平;利用德灵BN ProSpec特种蛋白分析仪检测血清超敏C反应蛋白(hs-CRP)水平。结果30例KD患儿大剂量丙种球蛋白静脉滴注前(静丙前)和滴注后(静丙后)血清slL-2R和hs-CRP水平与对照组比较差异均有统计学意义(P<0.01),静丙前和静丙后比较差异有统计学意义(P<0.01);静丙前KD患儿血清IL-6和对照组比较差异有统计学意义(P<0.01);KD患儿血清slL-2R与hs-CR P水平呈正相关(r=0.6,P<0.01),静丙前K D患儿血清IL-6和hs-CRP呈正相关(r=0.68,P<0.01)。结论血清IL-6和slL-2R参与了川崎病的发生,它们可作为判断预后、评估患儿免疫功能状况的参考指标。     

Interleukin-6 and its soluble receptor in patients with liver cirrhosis and hepatocellular carcinoma

AIM: To evaluate the immunohistochemical localization of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) on tumor tissue specimens from patients with hepatocellular carcinoma (HCC) and the serum levels of IL-6 and sIL-6R in a group of patients with HCC as well as liver cirrhosis (LC) in a group of patients with LC alone and in a control group. METHODS: Three groups of subjects were studied: groupⅠ(n=83) suffering from HCC and LC, groupⅡ(n=72) suffering from LC alone and groupⅢ(n=42) as healthy controls. All patients had hepatitis C virus infection. Serum IL-6 and IL-6R levels were determined using a commercially available ELISA kit. Immunohistochemistry was performed using the streptavidin-biotin complex and rabbit polyclonal antibodies against IL-6 and IL-6R. RESULTS: Immunohistochemistry analysis showed a medium to strong cytoplasmic and membrane reactivity for IL-6 and IL-6R respectively, in at least 40% of cases of HCC, whereas liver cirrhosis patients and controls were negative for IL-6 or showed a very mild and focal dot-like cytoplasmic reaction for IL-6R. Serum IL-6 levels in HCC group were significantly higher than those in LC and control groups (P<0.0001). There was no significant difference in sIL-6R concentrations among 3 groups. When the patients with HCC were divided into groups according to Okuda's classification, a significant serum increase of IL-6 and sIL-6R level was observed from stageⅠto stageⅢ(P<0.02,P<0.0005). When HCC and LC patients were divided into 3 classes of cirrhosis severity according to Child-Pugh, values in HCC patients were significantly higher than those in LC patients for each corresponding class (P<0.01). CONCLUSION: IL-6 serum levels in HCC patients are higher than those in LC patients and controls, suggesting an increased production of this cytokine by neoplastic cells. sIL-6R values are similar in all groups, increasing only in stageⅢHCC patients. These data suggest that they have a closer relationship with the neoplastic mass rather than with the residual functioning hepatic mass.     

Serum interleukin-6 levels and bone mineral density at the femoral neck in post-menopausal women with Type 1 diabetes.

BACKGROUND: Although osteopenia is often reported in Type 1 diabetes mellitus, the pathogenic mechanisms are not fully understood. Oestrogen deficiency also leads to decreased bone mineral density (BMD). Enhanced interleukin-6 (IL-6) production among Type 1 diabetic patients could be involved in the pathogenesis of diabetic bone loss since it is a potent bone resorbing cytokine. AIMS: To evaluate the relationship between serum bioactive IL-6 levels and BMD at the femoral neck of post-menopausal women with Type 1 diabetes. METHODS: We studied BMD, urine excretion of deoxypirydynoline crosslinks, serum bioactive IL-6 and soluble IL-6 receptor (sIL-6R) levels in 20 post-menopausal women with Type 1 diabetes mellitus, and compared these results with 20 matched healthy post-menopausal controls. RESULTS: Post-menopausal women with Type 1 diabetes had significantly lower BMD at the femoral neck and increased serum bioactive IL-6 levels compared with the control group, but no relationship was observed between these variables in a multiple regression analysis. Using BMD at the femoral neck of diabetic women as the dependent variable in the multiple step regression analysis model, we found that independent variables that were strongly associated with bone mass at the femoral neck in this group were: time since menopause and duration of diabetes. CONCLUSIONS: Although our study had a small sample size, we found that post-menopausal women with Type 1 diabetes mellitus present lower bone mass and higher serum bioactive IL-6 levels than matched healthy controls, but we were unable to find a correlation between these two parameters.     

Soluble interleukin-6 receptor as a prognostic factor in multiple myeloma

Interleukin-6 (IL-6) is a major growth factor for the clonal malignant plasma cells in multiple myeloma (MM). The effect of IL-6 may be enhanced by soluble IL-6 receptor (sIL-6R). As there is a clinical need for improved stratification of MM patients at diagnosis, we have studied the role of sIL-6R as a prognostic marker in 207 newly diagnosed MM patients. Serum sIL-6R concentration was above the upper reference limit in 47% of the patients at diagnosis. The concentrations of sIL-6R and two other prognostic factors, IL-6 and β-2 microglobulin (β2M), were all significantly higher in the patients who died within 3 years compared with those who survived. However, serum sIL-6R did not show linear correlation with IL-6 or β2M levels. In univariate logistic regression analysis sIL-6R was a significant predictor of 3-year mortality. Kaplan-Meier analysis showed that raised levels of sIL-6R were associated with shorter survival. When the patients were stratified into four groups according to their serum IL-6 and sIL-6R levels, the patients with normal serum levels of both parameters had clear survival benefit. As β2M was the most powerful prognostic factor in the multivariate analysis, the patients were also stratified according to their serum β2M and sIL-6R levels. The patients with raised levels of both β2M and sIL-6R had shorter survival than the patients in the other three groups. Thus, measurement of these parameters at diagnosis would help to stratify MM patients.     

Plasma interleukin-6 and renin substrate in reactive arthritis,rheumatoid arthritis,and systemic lupus erythematosus

Summary In order to study the role of interleukin-6 (IL-6) in inflammatory disease we monitored plasma levels of IL-6 and acute phase proteins such as C-reactive protein (CRP) and renin substrate (RS) in patients with reactive arthritis (ReA), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Venous plasma samples were collected: (1) during the acute phase or exacerbation of the disease, and (2) several months later during convalescense. Increased mean [95% confidence intervals (CI)] levels of plasma IL-6 were observed in patients with ReA both in the acute phase and later, 229 (177 to 280) ng/l and 197 (134 to 260) ng/l respectively (P <0.001 as compared to controls). The corresponding plasma IL-6 levels in RA patients were 283 (223 to 340) ng/l and 183 (151 to 226) ng/l, respectively (P <0.001 as compared to controls). Plasma IL-6 levels in SLE patients were not increased. Plasma RS levels were increased in all patient groups, but no significant correlation to IL-6 or CRP levels was observed, whereas plasma IL-6 and CRP levels showed a positive correlation in ReA and RA patients.     

高血压病超重及肥胖患者血清脂联素水平和IL-6含量的变化

目的研究高血压病超重及肥胖患者血清脂素水平、白介素-6(IL-6)含量的变化及其临床意义。方法63名正常非肥胖对照(男31名,女32名)和57名体重指数>25kg/m2的单纯性超重肥胖个体和41名高血压病超重肥胖患者进入研究,测量血压(BP)、体重指数(BMI)、腰围(WC)、腰臀围比(WHR),用ELISA法检测所有研究对象血清脂联素浓度、血清IL-6含量。结果单纯性超重肥胖患者与高血压超重病肥胖患者血清脂联素水平显著低于正常对照者[单纯性超重肥胖男性(7.03±1.67)mg/L,高血压病超重肥胖男性(6.13±1.74)mg/Lvs正常对照男性(8.21±0.93)mg/L,t=3.868,t=5.388,均P<0.01;单纯性超重肥胖女性(7.90±1.35)mg/L,高血压病超重肥胖女性(6.97±1.16)mg/Lvs正常对照女性(9.22±0.68)mg/L,t=4.612,t=7.167,均P<0.01]。高血压病超重肥胖男性血清IL-6含量显著高于正常对照男性[高血压病超重肥胖男性(394.86±353.9)pg/mlvs正常对照男性(248.02±223.2)pg/ml,t=2.368,P<0.05;高血压病超重肥胖女性(303.2±283.6)pg/mlvs正常对照女性(230.5±214.2)pg/ml,t=0.9046,P>0.05]。在高血压病超重肥胖患者中,脂联素与体重指数、腰围、腰臀围比、收缩压之间呈显著负相关;IL-6与收缩压之间呈显著正相关。结论脂联素水平下降与超重肥胖、血压之间存在一定的相关性;IL-6含量升高可能与高血压病有关。     

Serum Interleukin-6, Soluble Interleukin-6 Receptor and Crohn’s Disease Activity

The relationship between plasma interleukin-6 (IL-6) concentration and its soluble receptor in Crohn’s disease (CD) is not well elucidated. Twenty healthy volunteers and 94 consecutive patients with CD (44 in relapse and 50 in remission) were studied. Plasma IL-6 concentrations in patients with active disease [80 ± 9 pg/ml; mean ± standard error of the mean (SEM)] were significantly higher than in patients with inactive disease (50 ± 4 pg/ml; P < 0.001) or controls (3 ± 1 pg/ml; P < 0.001). However, concentrations did not vary with the severity of CD attacks. Plasma concentrations of soluble interleukin-6 receptor (sIL-6R) in active-CD patients (77 ± 5 ng/ml) did not differ significantly from those with inactive disease (82 ± 5 ng/ml), while both groups had significantly raised concentrations compared with those of controls (58 ± 6 ng/ml; P < 0.03 and P < 0.01, respectively). Plasma IL-6 concentrations correlated significantly with serum C-reactive protein (CRP) (r = 0.34; P < 0.001), whereas plasma sIL-6R concentrations did not. Taken together, these data suggest that, although IL6 and sIL6-R are both involved in the inflammatory process of CD, they are poor markers of disease activity.     

Changes in serum interleukin-6 and high-sensitivity C-reactive protein levels in patients with acute coronary syndrome and their responses to simvastatin

The role of inflammation in acute coronary syndrome (ACS) and the mechanism by which statin treats ACS is explored. Serum high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) levels were measured in 50 patients with ACS [including 30 cases with unstable angina (UA) and 20 patients with acute myocardial infarction (AMI)], 34 patients with stable angina (SA), and 30 controls. Patients in the ACS group were randomly assigned to a simvastatin group (including a simvastatin AMI subgroup, n = 11 and a simvastatin UA subgroup, n = 14) and a routine group (including a routine AMI subgroup, n = 9 and a routine UA subgroup, n = 16). The simvastatin group was given simvastatin 20mg/day and the routine group a placebo. After a 3-week follow-up, serum hs-CRP, IL-6 levels, and serum lipid concentrations were measured again. Both serum IL-6 and hs-CRP levels were significantly higher in the ACS group (including the UA and AMI subgroups) than in the SA and control groups (P < 0.001). After 3 weeks of treatment with simvastatin, the serum IL-6, hs-CRP, total cholesterol, and low-density lipoprotein cholesterol levels were decreased significantly in the simvastatin group (P < 0.001), but no significant changes were observed in the routine group. No relationship was observed between the rate of decrease of serum IL-6 or hs-CRP and serum lipids levels. The hs-CRP level showed a significant correlation with IL-6 by Spearmans rank correlation analysis (P < 0.01). Inflammation plays an important role in the initiation of ACS. Simvastatin possesses an anti-inflammatory effect, independent of its lipid-lowering action, which may play an important role in the early treatment of ACS.     

Indications of Low Sex Hormone Binding Globulin (SHBG) in Young Females with Type 1 Diabetes,and an Independent Association to Microalbuminuria

Sex hormone binding globulin (SHBG) is normally decreased during puberty and inversely related to insulin resistance. Microalbuminuria is rare before puberty in Type 1 diabetes implicating that sex hormones may contribute to its development. We investigated SHBG levels in young females with >5 years of Type 1 diabetes, and the association to microalbuminuria. Ten diabetic females with, and 15 without microalbuminuria, and 17 healthy controls in pubertal stage 4–5 were compared regarding anthropometric data, fasting serum levels of SHBG, testosterone, insulin, insulin-like growth factor-1 (IGF-1), lipids and lipoproteins. Multiple regression analyses were performed to study variables with independent influences on SHBG and albumin excretion rate (AER), respectively, in Type 1 diabetes. SHBG was lower and testosterone/SHBG ratio higher in normoalbuminuric females with diabetes than in controls. This was further emphasized in diabetic patients with microalbuminuria. IGF-1 was lower in Type 1 diabetes than in controls, and significantly decreased in microalbuminuric as compared to normoalbuminuric diabetic patients. IGF-1 was only correlated to SHBG in healthy controls. In Type 1 diabetes, applying stepwise multiple regression analysis, insulin dose, BMI, and HbA_1c had a significant and independent inverse influence on SHBG (r² = 0.77, p < 0.001). With log AER as the dependent variable, low SHBG, low IGF-1, HbA_1c, and age added to the regression (r² = 0.65, p = 0.004), whereas BMI, insulin dose and blood pressure did not. In conclusion, SHBG is decreased in young females with Type 1 diabetes, influenced by increased insulin requirements, BMI and HbA_1c. In turn, low SHBG seems to be independently associated to elevated AER in these patients. Prospective studies are necessary to confirm our results.     

Serum interleukin-6 levels in response to biologic treatment in patients with psoriasis

Objectives: Psoriasis is a chronic autoimmune disease involving a complex network of cytokines such as interleukin (IL)-6. We tested the hypothesis that serum IL-6 level is a useful indicator of disease activity and predicts the treatment response to biologics in patients with psoriasis.

Methods: We analyzed 113 psoriasis patients treated with biologics (73 with infliximab [IFX], 24 with adalimumab [ADA], and 16 with ustekinumab [UST]) in our hospital. Disease severity was assessed using the Psoriasis Area and Severity Index (PASI) score, and Disease Activity Score 28 based on C-reactive protein (DAS28-CRP).

Results: Before treatment, serum IL-6 levels significantly correlated with PASI scores in patients with psoriasis vulgaris (r?=?0.432, p?=?0.001) and with DAS28-CRP in patients with psoriatic arthritis (r?=?0.469, p?=?0.010). Serum IL-6 levels were significantly decreased by IFX (from 4.8 to 1.5) and ADA (from 2.5 to 1.4) therapy. In psoriatic arthritis, serum IL-6 levels at the endpoint tended to be lower in patients who achieved DAS28-CRP <2.3 (European League Against Rheumatism remission criteria) than in patients who did not.

Conclusion: Serum IL-6 level may be a useful biomarker for assessing disease activity in patients with psoriasis and for predicting responsiveness of joint symptoms to biologic treatment.     

Evaluation of inflammatory markers interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) in asthma

Introduction: Even though IL-6 and MMP-9 are associated with airway inflammation in asthma, there is paucity of data in Indian population. Objective: To determine the levels of IL-6 and MMP-9 in the serum of patients suffering from asthma, and correlate with (a) disease severity, as per GINA guidelines; (b) clinical phenotypes; and (c) response to treatment. Methodology: The levels of IL-6 and MMP-9 were compared between moderate persistent asthma (n = 25), severe persistent asthma (n = 25) and normal controls (n = 30). IL-6 and MMP-9 were measured by ELISA (R&D Systems Inc., USA and Canada) and compared between controls and asthmatics and between groups of different asthma severity, clinical variables, spirometry, and allergen sensitization. Spirometry was repeated after 2 months of ICS+LABA to assess response to treatment in relation to baseline IL-6 and MMP-9 levels. Results: We observed a significant difference in both IL-6 and MMP-9 levels among asthmatics versus controls (p < 0.001), moderate versus severe persistent asthma (p < 0.001). A significant negative correlation was observed between MMP-9 and pre-bronchodilator FEV₁ and FVC, but not with IL-6. There was no association between IL-6 and MMP-9 with asthma duration, total IgE, AEC, number of allergens sensitized and degree of sensitization. No significant correlation (p > 0.5) was observed with IL-6 and MMP-9 levels and FEV₁ improvement after 2 months of ICS+LABA. Conclusion: Higher levels of IL-6 and MMP-9 were observed in asthmatics as compared to controls and in severe persistent asthma as compared to moderate persistent asthma, higher levels of MMP-9 was associated with lower lung functions.     

Soluble interleukin-6 receptor (sIL-6R), a new prognostic factor in multiple myeloma

sIL-6R is a 55 kD soluble molecule mediating the interleukin-6 (IL-6) signal through the IL-6 receptor-associated transmembrane signal transducer, gp130. It has recently been suggested that sIL-6R serum levels may reflect disease severity in multiple myeloma (MM). We determined sIL-6R serum levels in 25 normal controls (NC) and in 80 MM patients at diagnosis and during the course of the disease. Measurements were done by ELISA. In NC, sIL-6R levels ranged from 14 to 40 ng/ml (median 28 ng/ml) whereas in MM patients the range was 10–200 ng/ml (median 38 ng/ml) ( P  < 0.01). 61 patients entered remission and 19 were resistant. Median sIL-6R value at diagnosis was 36 ng/ml (10–120) in responding patients, and 82 ng/ml (20–200) in non-responding patients ( P  < 0.001). During a follow-up from 12 to 89 months, sIL-6R values remained more or less stable in most patients. High sIL-6R levels correlated with poor survival.     

Detection of membrane and soluble interleukin-6 receptor in lymphoid malignancies

Summary. We studied the membrane expression of the gp80 chain of IL-6 receptor (IL-6R) by quantitative flow cytometry in chronic lymphocytic leukaemia (CLL) and leukaemic centrocytic lymphoma using a panel of seven monoclonal antibodies. IL-6R was detected in 18/26 CLL cases and 4/7 lymphoma cases, with a mean antigen density <3000 molecules/cell. Multiple labelling experiments confirmed the IL-6R expression by neoplastic cells. Specific mRNA was found by RT-PCR in neoplastic cells. A specific ELISA test was designed using two anti-IL-6 receptor MAbs to measure the serum soluble IL-6R (sIL-6R) in CLL (n = 48), B-cell non-Hodgkin's lymphoma (NHL; n = 40), and monoclonal gammopathy (MG; n = 32). SIL-6R was higher in CLL (170±12.6ng/ml) in NHL (160 ± 12ng/ml) and MG patients (183±23ng/ml) than in age-matched controls (100 ±5.6 ng/ml; P < 0.001) and higher in high-grade than low-grade NHL. No correlation was noted with a previous treatment. Among CLL cases the patients classified as stage B according to the Binet's staging of the disease had the highest sIL-6R values, thus suggesting a link with tumour cell mass.     

老年2型糖尿病患者颈动脉内膜中层厚度与白介素6的相关性

目的讨论2型老年糖尿病患者颈动脉内膜中层厚度与白介素（IL-6）的相关性。方法入选老年2型糖尿病患者,共71例,用超声检测颈动脉内膜中层厚度（IMT）,并检测血清IL6水平。按照颈动脉IMT进行分组。IMT〈1．0mm者分入IMT正常组,IMT≥1．0mm者分入IMT增厚组。对两组血清IL-6水平进行t检验,对IL-6与IMT进行相关性分析及Logistic回归分析。结果IMT增厚组IL-6水平（41．23±9．66ng／L）高于IMT正常组（31．53±9．23ng／L）,P〈0．01;IL-6与糖化血红蛋白及IMT均成正相关,R=0．351,P〈0．01;IL水平升高者颈动脉IMT增厚的风险增加5．57倍（OR=3．81,95％CI1．07～13．66,P〈0．05）。结论血清IL-6水平与颈动脉内膜中层厚度水平有关,并可作为老年2型糖尿病患者动脉粥样硬化程度的参考指标。     

Growth arrest-specific protein 6 (Gas6) as a noninvasive biomarker for early detection of diabetic nephropathy

Background: To investigate the diagnostic level of cystatin C and growth arrest-specific gene 6 (Gas6) levels in elderly type 2 diabetic patients with different degrees of diabetic nephropathy (DN). Methods: Four hundred and eighty-two old people, including 130 healthy controls, 130 normoalbuminuric diabetic patients, 122 with microalbuminuria, and 100 with macroalbuminuria, were recruited. Plasma Gas6 and serum cystatin C levels were measured. Results: Plasma Gas6 concentration was significantly lower in diabetic patients with microalbuminuria or macroalbuminuria, as compared with diabetic subjects with normoalbuminuria; while cystatin C was significantly higher. Gas6 was inversely correlated with BMI, WHR, and HbA1c, while cystatin C was inversely correlated with urea nitrogen and creatinine. Multivariate logistic regression analysis showed that, after adjusted for established diabetes risk factors, higher plasma Gas6 was significantly associated with a decreased risk of DN, while higher serum cystatin C was significantly associated with an increased risk. Receiver operating characteristic curve analysis showed that Gas6 was better than cystatin C as a biomarker for early diagnosis and detection of DN, with a cutoff value of 9.435 ng/mL (86.1% sensitivity and 84.6% specificity). Conclusion: Compared to cystatin C, Gas6 may be potentially a better noninvasive diagnostic biomarker for early detection of DN.