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.     

Elevated serum levels of neopterin in adult patients with polymyositis/dermatomyositis

We determined serum concentrations of neopterin, soluble tumour necrosis factor (55 kDa) receptor (sTNF-R) and soluble interleukin-2 receptor (sIL-2R) in plasma of 44 patients with polymyositis (PM)/dermatomyositis (DM), including 15 patients with primary PM, 13 patients with primary DM, and 16 patients with myositis and systemic sclerosis in overlap. Concentrations of neopterin, sTNF-R and sIL-2R were measured using commercially available immunoassays. Serum neopterin was increased in 35 of 44 PM/DM patients (80%), sTNF-R in 14 (32%) and sIL-2R in 18 (41%) patients, respectively. There were significant correlations between serum neopterin and sTNF-R, sIL-2R and erythrocyte sedimentation rate (all P < 0.001). Neopterin, as well as sTNF-R and sIL-2R, did not correlate with clinical (neuromuscular and activities of daily living scores) and laboratory (creatine kinase levels) manifestations of myositis. Increased serum levels of neopterin were associated with non-muscular manifestations of PM/DM. In conclusion, serum neopterin appears to be a useful laboratory marker for ongoing immune activation and global disease activity in PM/DM.      

The combination of IL-6 and its soluble receptor is associated with the response of rheumatoid arthritis patients to tocilizumab

BackgroundIL-6 contributes significantly to the chronic inflammatory process of rheumatoid arthritis (RA). Tocilizumab, a humanized anti-human IL-6 receptor antibody that blocks the signaling originated by the IL-6/IL-6R complex, is an effective treatment. However, predictors of the response to tocilizumab are still required. We aimed to combine IL-6 and soluble IL-6R (sIL-6R) levels to identify groups of responses.MethodsHeparinized blood and clinical data from 63 RA patients were collected before treatment and after 3 and 6 months. Two-step clustering (SPSS v.18) was used to establish the relationship between IL-6 and sIL-6R. Then, we compared European League Against Rheumatism (EULAR) response criteria with remission achievement in the groups of patients.ResultsThree statistical significant clusters of RA patients (i.e., g1, g2, and g3) were defined by serum concentrations of IL-6 and sIL-6R at baseline. All groups of RA patients had higher IL-6 and sIL-6R levels than healthy donors. The levels of IL-6 expressed as median (IQR) in g1 patients were 124(90–183) pg/ml, in g2 12.3(4.4–24) pg/ml, and in g3 60.1(30–146) pg/ml (p < 0.001). The levels of sIL-6R expressed as mean ± sd in g1 patients were 250.5 ± 72 ng/ml, in g2 269.1 ± 125 ng/ml, and in g3 732.7 ± 243 ng/ml (p < 0.001). Disease activity score (DAS)28, C-reactive protein, and erythrocyte sedimentation rate were comparable in the three groups at baseline. Disease duration in g3 was the longest (median(IQR) years: g1 = 11(5–15), g2 = 12(8–20), and g3 23(16–26); p = 0.006), with years of disease evolution being correlated with sIL-6R levels (R = 0.417, p < 0.001). Simple and Clinical Disease Activity Index (SDAI and CDAI) decreased significantly in the three groups. However, EULAR response criteria and remission achievement at 6 m was different in the three groups (p = 0.03 and 0.04, respectively). In all. 17 out of the 18 patients in g1 had a good or moderate response to tocilizumab. Conversely, the percentage of patients with no response to tocilizumab was higher in g3 than in g1 and g2. We also observed different changing patterns of IL-6 and sIL-6R levels among the three groups.ConclusionsRA patients could be easily stratified prior to therapeutic intervention with two molecules related to the pathway blocked by tocilizumab. G1 patients, who had the best response to tocilizumab, had the highest level of IL-6 and the lowest level of sIL-6R.     

Circulating Soluble Interleukin-2 Receptor α and β Chain in Inflammatory Bowel Disease

Objectives : Inflammatory bowel disease is characterized by T cell activation. Activated T cells shed interleu-kin-2 receptors (IL-2R) in a soluble form. A positive correlation between sIL-2Rα (CD25) and disease activity in inflammatory bowel disease has been shown previously, whereas IL-2Rβ (CD122) has never before been investigated in this respect. Serum from 27 patients with ulcerative colitis (UC), 31 with Crohn's disease (CD), and 29 healthy volunteers was obtained. Methods : Disease activity was scored according to a semiquantitative score for UC and by Crohn's disease activity index for CD. sIL-2Rα and -β chains were assessed by a sandwich ELISA technique using monoclonal antibodies specific for CD25 and CD122, respectively. Results : The median concentration of sIL-2Rα was 4424 pg/ml in healthy controls, 6460 in UC ( p < 0.004), and 6371 in CD ( p < 0.01). The corresponding value of sIL-2Rβ in healthy volunteers was 605 pg/ml; in active UC, significantly lower levels were found at 233 pg/ml ( p < 0.01), whereas in inactive UC, no such difference was observed at 725 pg/ml ( p > 0.05). In CD, the levels were 839 pg/ml in inactive and 920 pg/ml in active disease stages ( p > 0.05 vs controls). A positive and significant correlation existed between sIL-2R levels of α and β chains in CD ( r = 0.64; p < 0.01) but not in UC ( r = -0.32; p > 0.05) or in healthy volunteers ( r = 0.16; p > 0.05). Conclusion : Future longitudinal studies will be necessary to learn whether this newly assessed sIL-2Rβ (CD122), which may interfere with IL-15R, could be used to predict disease exacerbation and to monitor anti-inflammatory therapy in UC.     

Plasma levels of tumor necrosis factor-α and its receptors in patients with mitral stenosis and sinus rhythm undergoing percutaneous balloon valvuloplasty

This study aimed to determine whether plasma levels of tumor necrosis factor-α (TNF-α) and soluble TNF receptor (sTNF-R) increases in rheumatic mitral stenosis (MS) patients with sinus rhythm and to examine the effect of percutaneous mitral balloon valvuloplasty (PMBV) on these parameters. Twenty-six patients with MS and sinus rhythm (study group, 20 female, mean age 33 ± 8 years), who were scheduled for PMBV, and a well-matched control group consisting of 21 healthy volunteers (15 female, mean age 35 ± 6 years) were enrolled in the study. Tumor necrosis factor-α and sTNF-R levels were compared between study patients and controls, and between peripheral and left atrium (LA) blood. Changes in TNF α and sTNF-R levels 24 h and 4 weeks after PMBV were analyzed. Significantly higher baseline TNF-α and sTNF-R levels were noted in the study group. In the study group, TNF-α and its receptors were also found to be higher in LA blood than in baseline peripheral blood. After PMBV, mitral valve area (MVA) increased and transmitral pressure gradient decreased significantly. At the 24th hour after PMBV, the TNF-α level decreased from 29.61 ± 12.22 pg/ml to 22.42 ± 8.81 pg/ml (P < 0.0001) and at the 4th week, from 22.42 ± 8.81 pg/ml to 18.92 ± 7.37 pg/ml (P < 0.0001). Similar reductions were observed in the sTNF-R level. Regression analysis between the difference in sTNF-R level measured 24 h after and before PMBV and the difference in MVA measured 24 h after and before PMBV showed a significant direct relationship between these variables. This study suggests that isolated rheumatic MS without atrial fibrillation is accompanied by increased TNF-α and sTNF-R level. The successful PMBV establishes a significant reduction in TNF-α and its receptors, probably due to improved postprocedural hemodynamic parameters.     

Serum interleukin-26 is a promising biomarker in systemic lupus erythematosus patients: Particular relation to disease activity and nephritis

Aim of the workTo investigate the clinical utility of serum interleukin-26 (IL-26) in patients with systemic lupus erythematosus (SLE).Patients and methodsThe study was carried out on 42 SLE patients and 42 matched controls. SLE disease activity index 2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI) were assessed. Serum IL-26 was measured.ResultsThe mean age of patients was 28.8±11.4 years with 78.6% females. 76.2% of patients were active; 7.1% very-high grade, 45.2% high, 16.7% moderate and 31% mild. 42.9% of patients had nephritis. The mean SLEDAI-2K was 10.4±6.4 and SLICC-DI 1.19±1.15. IL26 level was significantly higher in patients (64±76.4 pg/ml) compared to control (8.7±2.6 pg/ml), in active cases (79.2±81.9 pg/ml) compared to those inactive (15.3±4.8 pg/ml) and in those with nephritis (n = 18) (113.4±92.2 pg/ml) compared to those without (n = 24) (23.1±7.6 pg/ml).IL-26 level was significantly higher among cases receiving both steroids and mycophenolate mofetil than those receiving steroids with azathioprine (p = 0.005). There was a significant negative correlation between IL26 and serum albumin, hemoglobin and complement 3 (C3) levels (p < 0.001, p < 0.001 and p = 0.006 respectively). There was also a significant correlation between IL26 and both SLEDAI-2K (r = 0.95, p < 0.001) and SLICC-DI (r = 0.68, p < 0.001). At cut off value 16.3 pg/ml, IL26 differentiated patients and control; sensitivity 90.5%, specificity 100% (F. 2) and at 20 pg/ml detects active from non-active; sensitivity and specificity 100%.ConclusionIL-26 is a promising biomarker of SLE with high sensitivity and specificity. There is a relation of IL-26 with disease activity, damage and nephritis.     

Serum IL-33 levels are raised in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis

To determine serum interleukin-33 (IL-33) levels and their associations with clinical parameters in patients with systemic sclerosis (SSc). Serum IL-33 levels were examined by enzyme-linked immunosorbent assay in 69 patients with SSc and 30 healthy individuals. In a retrospective longitudinal study, sera from 14 patients with SSc were analyzed (follow-up, 1–7 years). Serum IL-33 levels were elevated in SSc patients (261.7 ± 141.9 pg/ml) compared with healthy individuals (174.9 ± 72.4 pg/ml; P < 0.001). Patients with diffuse cutaneous SSc had higher levels of IL-33 (287.5 ± 146.6 pg/ml) than those with limited cutaneous SSc (221.5 ± 126.5 pg/ml; P < 0.05). Pulmonary fibrosis and decreased forced vital capacity were more commonly found in patients with elevated IL-33 levels than in those with normal IL-33 levels. IL-33 levels correlated positively with the extent of skin sclerosis, and inversely with percent predicted forced vital capacity. IL-33 levels were increased in SSc patients and correlated with the extent of skin sclerosis and the severity of pulmonary fibrosis. Therefore, IL-33 possibly plays a role in cutaneous and pulmonary fibrosis in SSc patients.     

Evaluation of interleukin-6 and its soluble receptor components sIL-6R and sgp130 as markers of inflammation in inflammatory bowel diseases

Purpose

Interleukin-6 (IL-6) production and signalling are increased in the inflamed mucosa in inflammatory bowel diseases (IBD). As published serum levels of IL-6 and its soluble receptors sIL-6R and sgp130 in IBD are from small cohorts and partly contradictory, we systematically evaluated IL-6, sIL-6R and sgp130 levels as markers of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC).

Methods

Consecutive adult outpatients with confirmed CD or UC were included, and their disease activity and medication were monitored. Serum from 212 CD patients (815 measurements) and 166 UC patients (514 measurements) was analysed, and 100 age-matched healthy blood donors were used as controls.

Results

IL-6 serum levels were significantly elevated in active versus inactive CD and UC, also compared with healthy controls. However, only a fraction of IBD patients showed increased serum IL-6. IL-6 levels ranged up to 32.7 ng/mL in active CD (>?5000-fold higher than in controls), but also up to 6.9 ng/mL in inactive CD. Increases in active UC (up to 195 pg/mL) and inactive UC (up to 27 pg/mL) were less pronounced. Associations between IL-6 serum levels and C-reactive protein concentrations as well as leukocyte and thrombocyte counts were observed. Median sIL-6R and sgp130 levels were only increased by up to 15%, which was considered of no diagnostic significance.

Conclusions

Only a minority of IBD patients shows elevated IL-6 serum levels. However, in these patients, IL-6 is strongly associated with disease activity. Its soluble receptors sIL-6R and sgp130 do not appear useful as biomarkers in IBD.

     

Serum levels of soluble interleukin-2 receptor

Objective. To determine whether circulating serum levels of soluble interleukin-2 receptor (sIL-2R) are elevated in patients with localized scleroderma, and if levels of sIL-2R can differentiate between active and inactive disease. Methods. Seventeen patients with localized scleroderma were categorized by overall physician assessment into active, inactive, and indeterminate groups, according to disease activity. Serum sIL-2R levels were analyzed and correlated with disease activity. Results. The mean sIL-2R level was significantly higher (P = 0.005) in those with active disease (1,675 ± 823 units/ml) than in those with inactive disease (722 ± 218 units/ml). Conclusion. Serum sIL-2R levels are elevated in patients with localized scleroderma. When present, elevated sIL-2R levels appear to be able to differentiate active from inactive disease. This fact also suggests cell-mediated immune activation in this condition. Further serial studies are required to assess the value and sensitivity of sIL-2R levels in measuring changes in disease activity.     

Interleukin-18 as a mediator of systemic juvenile idiopathic arthritis

The objective of this report is to explore the balance between serum and synovial fluid levels of interleukin (IL)-18 in children with juvenile idiopathic arthritis (JIA). Blood samples were obtained from 81 children with JIA and 18 control children. Synovial fluid samples were collected from 16 children with oligoarticular JIA. Concentrations of IL-18 were determined using commercial kit. Patients with systemic JIA had higher serum levels of IL-18 than patients with other forms of JIA or control children, both during the active (median, range: 6,240, 1,600–78,750 pg/ml) and inactive (1,615, 513–3,270 pg/ml) phase of disease [analysis of variance (ANOVA), P < 0.05). Levels of IL-18 in sera of children with oligoarticular JIA (255, 89–4,342 pg/ml) were similar to the respective synovial fluid levels (217, 89–1,245 pg/ml). Serum levels of IL-18 were proportional to the erythrocyte sedimentation rate and levels of C-reactive protein, but inversely proportional to the haemoglobin levels. IL-18 appears to be an important mediator of systemic JIA, while it seems of a lesser relevance in pathogenesis of other JIA forms. Therefore, inhibition of IL-18 might be a base for a successful biological therapy for systemic JIA.     

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.     

Plasma interleukin-10 and interleukin-12 levels in patients with familial Mediterranean fever

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of fever, polyserositis and arthritis. A vast array of cytokines were analysed in these patients, however, little is known about the pro-inflammatory cytokine interleukin (IL)-12. Plasma IL-12 and IL-10 were measured in 24 patients with FMF (19 active, 5 inactive) and 18 healthy controls by ELISA. From 15 active patients blood was also drawn in attack-free period. Mean plasma IL-12 levels of the FMF patients (mean ± SEM, 6.84±3.59 pg/ml) were higher than the controls (0.13±0.09 pg/ml, P<0.001). Mean IL-12 levels of active (7.02±5.23 pg/ml) and inactive patients (6.89±5.61 pg/ml) were comparable, and they were higher compared to controls (P≤0.001). Mean plasma IL-10 levels of the total FMF patients (3.01±1.53 pg/ml) were also higher than the controls (P=0.024). Patients had higher IL-10 levels in attacks (3.83±2.02 pg/ml) compared to levels when they were in remission (1.86±1.59 pg/ml, P=0.046). Significantly elevated IL-12 levels in FMF patients regardless of activity may suggest the presence of a pro-inflammatory state also in the inactive period of FMF. Significant increase in IL-10 levels in FMF group may point to the compensatory suppression of inflammation in active periods of the disease.     

Interleukin-6 Blood Levels in Sensitive and Multiresistant Tuberculosis

Abstract Background:   Interleukin-6 (IL-6) is a proinflammatory cytokine implicated in the immunopathogenesis of tuberculosis (TB). Multidrug resistance in tuberculosis is recognized worldwide as an important public health issue. The mechanism underlying TB pathogenesis in general and drug resistance in particular is not well understood, but it may be that IL-6 is one factor that enhances pathology in drug-resistant TB. The purpose of this study was to identify patterns of IL-6 production in active pulmonary TB with different sensitivity to standard drug therapy. Patients and Methods:   IL-6 blood levels were studied in 38 patients with active pulmonary TB: 23 patients were very sensitive to specific chemotherapy (STB), and 15 were multiresistant (MDRTB). An ELISA assay (Biossource) was used to quantify IL-6 in the sera of 38 TB patients and 63 healthy blood donors. Results:   The STB group was composed of 16 males (73.9%) and 7 females, MDRTB by 9 males (60%) and 6 females, and control group by 51 males (81%) and 12 females. The results showed a significant increase in IL-6 concentration in TB (median = 4.3 pg/ml, range 0.5–24) compared to that of healthy individuals (median = 0.5 pg/ml, range 0–2.8, p < 0.001). Additionally, IL-6 concentrations were increased in both STB (median = 4.1 pg/ml, range 0.5–24) and MDRTB (median = 5.1 pg/ml, range 0.5–12) groups in relation to controls (p < 0.001). In contrast, significant differences were not observed between STB and MDRTB groups (p > 0.05). Conclusion:   IL-6 levels were increased in pulmonary tuberculosis, independent of drug resistance.     

Serum levels of natriuretic peptides in patients with Behcet’s disease

The objective of our study was to elucidate serum levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) in Behcet’s disease (BD) patients with active and inactive period. The multicenter study included 53 patients with active (n = 28) and inactive (n = 25) BD (mean age, 34.3 ± 9 years; 15 men and 38 women) satisfying the International Study Group criteria and 26 healthy controls (mean age, 34.4 ± 6.1 years; seven men and 19 women) matched for age and gender from a similar ethnic background. Serum natriuretic peptides levels were determined by enzyme immunoassay kit. Mean serum ANP concentrations in the active patients (4.01 ± 1.21 ng/ml) were significantly lower than in the healthy controls (5.76 ± 1.99 ng/ml, p = 0.004). Mean serum BNP levels were found to be significantly higher in both the active (6.19 ± 2.97 ng/ml) and inactive (6.49 ± 2.88 ng/ml) BD groups compared with the control group (3.82 ± 1.1 ng/ml, p = 0.004 and p = 0.001, respectively). Mean serum CNP concentrations in the active patients (0.49 ± 0.12 ng/ml) were significantly lower than in the inactive patients (0.65 ± 0.2 ng/ml, p = 0.017) and the healthy controls (0.8 ± 0.27 ng/ml, p < 0.001). Our results suggest that changes in natriuretic peptide levels may be associated with vasculitis that play role in the etiopathogenesis of the BD.     

Elevated Levels of Type II Soluble Tumor Necrosis Factor Receptors in the Bronchoalveolar Lavage Fluids of Patients with Sarcoidosis

Since tumor necrosis factor (TNF) is known to be involved in granuloma formation in sarcoidosis, and soluble TNF receptors (sTNF-Rs) inhibit TNF action in vivo, we evaluated the levels of sTNF-Rs in the bronchoalveolar lavage fluids (BALF) of 31 subjects using an enzyme-linked immunosorbent assay. Our group consisted of 13 patients with sarcoidosis (7 sarcoidosis patients who received no treatment and 6 who received corticosteroid therapy) and 18 control subjects (11 healthy nonsmokers and 7 asymptomatic smokers). Type II (75-kDa), but not type I (55 kDa) sTNF-R in BALF was elevated significantly in patients with sarcoidosis compared with the healthy nonsmokers (type I: 126.7 ± 17.6 pg/ml BALF vs 79.4 ± 16.5 pg/ml BALF, p > 0.05; type II: 98.3 ± 27.8 pg/ml BALF vs 26.7 ± 4.9 pg/ml BALF, p < 0.05). Although levels of type I sTNF-R in BALF from sarcoidosis patients were not correlated with any cellular profiles of BALF, concentrations of type II correlated significantly with the numbers of lymphocytes in BALF. We concluded that sTNF-R is a normal constituent of the epithelial lining fluids and that levels of type II sTNF-R are elevated significantly in the BALF from individuals with sarcoidosis. This suggests that sTNF-Rs may influence the local bioactivity of TNF and may also contribute to the pathogenesis of sarcoidosis. Accepted for publication: 7 November 1996     

The effects of adalimumab and methotrexate treatment on peripheral Th17 cells and IL-17/IL-6 secretion in rheumatoid arthritis patients

Objective of the study is to assess the effects of adalimumab and MTX therapy on peripheral Th17 cells and IL-17/IL-6 secretion in RA patients. Twenty active RA patients were treated with oral MTX 15 mg per week (MTX group, n = 10), or hypodermal adalimumab 40 or 80 mg every other week (ADA group, n = 10). Peripheral blood samples were taken for laboratory evaluation at week 0 and week 12 of treatment, including flowcytometric detection of peripheral CD4(+) IL-17(+) cells, RT-PCR detection of mRNA expressions of IL-17, RORc and FoxP3, and ELISA determination of serum IL-17 and IL-6. Ten age and sex marched healthy volunteers were included as normal controls. Results showed that (1) DAS28 in both groups improved at week 12 compared to week 0 (3.9 ± 1.3 vs. 6.4 ± 1.4 and 3.2 ± 0.9 vs. 5.2 ± 0.9, respectively). (2) The percentage and MFI of peripheral CD4(+) IL-17(+) cells in RA patients were significantly higher comparing to normal controls (1.64 ± 0.97% vs. 0.75 ± 0.20%, p < 0.01; and 29.8 ± 9.7 vs. 19.8 ± 4.6, p < 0.05, respectively), and positively correlated with ESR and DAS28. Peripheral Th17 cells and serum IL-6 in RA patients decreased after treatment (from 1.60 ± 0.78% to 1.28 ± 0.41%, and from 17.15 ± 14.53 pg/ml to 6.97 ± 5.51 pg/ml, p < 0.05, respectively). Peripheral FoxP3 mRNA expression in active RA patients was significantly lower comparing to normal controls, and negatively correlated with ESR. Baseline Th17 percentage of RA patients negatively correlated with DAS28 improvement after treatment. In conclusion, adalimumab and MTX treatment down regulates peripheral Th17 cells and serum IL-6 level in RA patients. Baseline Th17 level negatively predicts the effect of adalimumb/MTX treatment.     

肺结核患者支气管肺泡灌洗液中某些细胞因子与受体的检测及其临床意义

目的 研究肺结核患者支气管肺泡灌洗液(BALF)中TNF-α及受体、IL-1β及受体的特征及其临床意义,并探讨其在结核病免疫发病中的作用.方法 采用双抗体夹心ABC-ELISA法检测46例活动性肺结核患者、21例非活动性肺结核患者BALF及血清和20例健康者血清TNF-α、可溶性TNF受体(sTNF-R)Ⅰ、IL-1β、IL-1受体水平,对其中19例活动性肺结核患者抗结核治疗后的上述细胞因子水平进行随访.组间比较采用t检验.结果 活动性肺结核组BALF中TNF-α、sTNF-R Ⅰ、IL-1β、IL-1受体水平及TNF-α/sTNF-R Ⅰ比值分别为(286.2±96.3)、(2 431.5±1 124.6)、(58.6±3.2)、(162.4±17.1)pg/L和0.06±0.01,显著高于非活动性肺结核组(t值分别为3.36、3.25、2.95、2.27和3.12,均P<0.05).空洞组BALF中TNF-α、sTNF-R Ⅰ、IL-1β、IL-1受体水平及TNF-α/sTNF-R Ⅰ比值分别为(381.4±106.4)、(2 824.7±1 318.5)、(66.4±4.6)、(176.4±18.7)pg/L和0.07±0.01,均显著高于无空洞组(t值分别为3.46、2.37、3.19、2.99和3.22,均P<0.05).抗结核治疗2个月末,19例患者中有16例患者BALF中TNF-α、sTNF-RI、IL-1β、IL-1受体水平及TNF-α/sTNF-R Ⅰ比值较治疗前明显降低(t值分别为3.26、3.17、3.28、2.92和3.12,均P<0.01),且上述患者临床症状改善,痰菌阴转,胸部X线片病灶吸收、空洞缩小或闭合.结论 TNF-α、sTNF-R Ⅰ、IL-1β、IL-1受体等均参与结核病免疫发病过程.肺结核患者BALF中TNF-α、sTNF-R Ⅰ、IL-1β、IL-1受体水平的检测可作为了解疾病活动性、判断病情及预后、监测抗结核疗效的参考.     

Serum and synovial fluid levels of interleukin-17 in correlation with disease activity in patients with RA

The aim of this study was to evaluate serum and synovial levels of IL-17A by ELISA in rheumatoid arthritis (RA) and find out the correlations between IL-17A levels and various clinical, laboratory parameters and RA disease activity and severity indices. Group I consists of 30 adult active RA patients fulfilling the ARA 1987 revised criteria, with knee effusion and receiving basic therapy, and with a mean age of 41.47 ± 11.49 years and mean disease duration of 9.5 ± 4.16 years. Group II consisted of 13 healthy volunteers, age- and sex-matched, with a mean age of 39.08 ± 14.19 years. RA patients showed significantly higher mean serum IL-17A levels than controls (11.25 ± 9.67 vs. 0.6 ± 1.4 pg/mL, respectively, p = 0.0002). Synovial IL-17A levels showed a significant positive correlation with serum IL-17A levels (r = 0.5 and p = 0.005). RA patients with negative rheumatoid factor (RF) had non-significantly higher mean serum IL-17A levels (12 ± 9.86 pg/mL) compared to those with positive RF (10.82 ± 9.81 pg/mL); however, the mean synovial IL-17A levels were nearly the same. Significant positive correlations were found between both serum and synovial IL-17A levels and DAS-28 scores (r = 0.556, 0.392 and p = 0.001, 0.032, respectively). RA patients with class III functional status showed significantly higher mean serum IL-17A levels (17.53 ± 13.43 pg/mL) than classes I and II (8.97 ± 6.97 pg/mL, p = 0.009). These led us to conclude that the elevated serum and synovial IL-17A levels in RA patients parallel the degree of disease activity and severity. This may highlight the usefulness of IL-17 (especially serum level) as a possible marker for more aggressive joint involvement and damage.     

Increased mucosal concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), sE-selectin,and interleukin-8 in active ulcerative colitis

Cell surface adhesion molecules (CAM) are important promotors of the immunoinflammatory cascade. The circulating levels of soluble intercellular adhesion molecule 1 (ICAM-1) have previously been shown to correlate with disease activity in inflammatory bowel disease. The primary aim of this study was consequently to investigate if this also applies to mucosal levels of soluble ICAM-1. We measured soluble ICAM-1 levels in intestinal biopsy specimens and the endoscopic activity of 69 patients with ulcerative colitis (UC) and 14 controls and found that the median concentration of soluble ICAM-1 was significantly higher in patients with moderately or very active UC (15.0 ng/ml) as compared to slightly active (9.8 ng/ml) and inactive UC (9.5 ng/ml) as well as controls (6.5 ng/ml) (P<0.005). To further elucidate the interactions, two other CAM [E-selectin and vascular cellular adhesion molecule 1 (VCAM-1)], together with interleukin-8 (IL-8), IL-2 receptor (IL-2R)α andβ chains, were also measured. A significant trend towards higher soluble E-selectin levels in biopsies with active UC (1.8 pg/ml) as compared to inactive UC (1.3 pg/ml) and to controls (<1.0 pg/ml) (P<0.01) was also found. In contrast, soluble VCAM-1 was barely detectable in biopsies from two UC patients. A significant correlation was found between soluble ICAM-1 and IL-8 concentrations (r=0.46;P<0.0001), and between sICAM-1 and sIL-2Rα concentrations (r=0.69;P<0.0001), while sIL-2Rβ was not detected. This study shows that intestinal ICAM-1 and E-selectin correlate with endoscopic activity of UC and with IL-8 and IL-2Rα levels. These mediators may be useful in monitoring mucosal inflammation in studies exploring the therapeutical potential of targeting CAM. The lack of detectable VCAM-1, which is induced only in venous endothelium is interesting. It may suggest that intestinal inflammation mainly affects arterial endothelial cells and support the theory that intestinal vasculitis is involved in the pathogenesis of inflammatory bowel disease.