Angiogenic Activity of Sera from Pulmonary Tuberculosis Patients in Relation to IL-12p40 and TNFα Serum Levels

The role of angiogenesis in the pathogenesis of tuberculosis (TB) is not clear. The aim of this study was to examine the effect of sera from TB patients on angiogenesis induced by different subsets of normal human mononuclear cells (MNC) in relation to IL-12p40 and TNFα serum levels. Serum samples from 36 pulmonary TB patients and from 22 healthy volunteers were evaluated. To assess angiogenic reaction the leukocytes-induced angiogenesis test according to Sidky and Auerbach was performed. IL-12p40 and TNFα serum levels were evaluated by ELISA. Sera from TB patients significantly stimulated angiogenic activity of MNC compared to sera from healthy donors and PBS (p < 0.001). The number of microvessels formed after injection of lymphocytes preincubated with sera from TB patients was significantly lower compared to the number of microvessels created after injection of MNC preincubated with the same sera (p < 0.016). However, the number of microvessels created after the injection of lymphocytes preincubated with sera from healthy donors or with PBS alone was significantly higher (p < 0.017). The mean levels of IL-12p40 and TNFα were significantly elevated in sera from TB patients compared to healthy donors. We observed a correlation between angiogenic activity of sera from TB patients and IL-12p40 and TNFα serum levels (p < 0.01). Sera from TB patients constitute a source of mediators that participate in angiogenesis and prime monocytes for production of proangiogenic factors. The main proangiogenic effect of TB patients’ sera is mediated by macrophages/monocytes. TNFα and IL-12p40 may indirectly stimulate angiogenesis in TB.     

Serum vascular endothelial growth factor in cyanotic congenital heart disease functionally contributes to endothelial cell kinetics in vitro

BackgroundRemarkable amounts of neovascularization develop in patients with cyanotic congenital heart disease who have low pulmonary blood flow and systemic cyanosis, but the factors functionally responsible for angiogenesis in cyanotic congenital heart disease have not been determined.Methods and resultsTo investigate the functional angiogenic molecules in serum from these patients, serum angiogenic activity was studied in 21 patients (systemic oxygen saturation: 82 ± 1.9%) and in 17 healthy controls. Patient serum was more active in stimulating the tube formation of human umbilical vein endothelial cells (HUVECs) into capillary-like structures than control serum (150% vs 104% of internal control; p < 0.001). This increased serum angiogenic activity normalized after total cardiac repair (p < 0.001). The migration activity of HUVECs was also accelerated in patient serum (p = 0.007). To identify the molecules in patient serum affecting tube formation of HUVECs, we examined the effects of an inhibitor or a neutralizing antibody against various angiogenic molecules on in vitro angiogenesis. Both the soluble vascular endothelial growth factor (VEGF) receptor 1 and the VEGF receptor 2 tyrosine kinase inhibitor SU5416 reduced the basal serum angiogenic activity of patients and this was reversed by a supplement of recombinant human VEGF.ConclusionOur results indicate that serum VEGF functionally contributes to vascular endothelial cell kinetics in patients with cyanotic congenital heart disease.     

Pulmonary Artery Dimensions as a Prognosticator of Transplant-Free Survival in Scleroderma Interstitial Lung Disease

Background

Systemic sclerosis is a chronic debilitating autoimmune disease characterized by endothelial dysfunction and multi-organ fibrosis. Interstitial lung disease, a common manifestation of SSc, is termed scleroderma-related interstitial lung disease (SSc-ILD) and along with pulmonary hypertension contributes to a majority of deaths in SSc. SSc-ILD patients frequently develop pulmonary hypertension, which prognosticates a poorer outcome. We investigated pulmonary artery dimensions as an outcome predictor in patients with SSc-ILD.

Methods

A retrospective chart review abstracting data from SSc-ILD patients evaluated at a large tertiary care center was performed. HRCT imaging was reviewed and pulmonary artery (PA) and ascending aorta (Ao) diameters were measured for calculation of the PA:Ao ratio. Additionally, demographics, vital signs, spirometric parameters, comorbidities, and mean pulmonary artery pressures were collected when available. Outcome analysis with lung transplant or death events within 4 years based on pulmonary artery size as well as PA:Ao ratio was performed.

Results

70 SSc-ILD patients were identified. Mean pulmonary artery diameter and PA:Ao ratio was 31.17 and 1.07 mm, respectively. Patients with a pulmonary artery diameter ≥32 mm had higher risk of lung transplantation or death (p < 0.001) within 4 years. Patients with a PA:Ao ratio ≥1.1 also had higher risk of lung transplantation or death (p < 0.001) within 4 years. Unadjusted outcomes analyses also identified PA:Ao ratio ≥1.1 as an independent outcome predictor (hazard ratio 3.30, p < 0.001).

Conclusions/Clinical implications

In SSc-ILD patients, a PA:Ao ratio ≥1.1 is associated with higher risk of lung transplant or death. These data suggest that PA:Ao dimension may be used for prognostication in SSc-ILD.

     

Angiogenesis regulatory factors in the vitreous from patients with proliferative diabetic retinopathy

We determined the levels of the endogenous angiogenesis inhibitors soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), thrombospondin (TSP)-1 and TSP-2 in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and correlated their levels with clinical disease activity and the levels of vascular endothelial growth factor (VEGF). Vitreous samples from 30 PDR and 25 nondiabetic patients were studied by enzyme-linked immunosorbent assay. TSP-1 was not detected. VEGF and TSP-2 levels were significantly higher in PDR with active neovascularization compared with inactive PDR and nondiabetic patients (P < 0.001 for both comparisons). VEGF, sVEGFR-1 and TSP-2 levels were significantly higher in PDR with hemorrhage compared with PDR without hemorrhage and nondiabetic patients (P = 0.0063; 0.0144; <0.001, respectively). VEGF and sVEGFR-1 levels were significantly higher in PDR without traction retinal detachment (TRD) compared with PDR with TRD and nondiabetic patients (P = 0.038; 0.022, respectively). TSP-2 levels were significantly higher in PDR with TRD compared with PDR without TRD and nondiabetic patients (P < 0.001). There was a significant correlation between levels of VEGF and sVEGFR-1 (r = 0.427, P = 0.038). Our findings suggest that upregulation of sVEGFR-1 and TSP-2 may be a protective mechanism against progression of angiogenesis associated with PDR. TSP-2 might be associated with TRD.     

Clinical significance of Angiopoietin-1 in Behcet’s disease patients with vascular involvement

Behcet’s disease (BD) is a chronic multisystem inflammatory disorder of unclear etiology. Vascular inflammation, endothelial dysfunction and angiogenesis may be in part responsible for the pathogenesis of BD. Angiopoietin-1 (Ang-1) is a recent angiogenic mediator. The aim of the present study was to assess Ang-1 in the plasma of BD patients as well as to analyze its association with clinical, and laboratory parameters of the disease. The present study included 47 BD patients and 30 age- and gender-matched healthy controls. Demographic, clinical, disease activity and severity were prospectively assessed. Plasma Ang-1 levels were measured using enzyme-linked immunosorbent assay. The plasma level of Ang-1 in BD patients was significantly lower than healthy controls (p = 0.005). Plasma Ang-1 level in patients with vascular affection was significantly lower than those without vascular affection (p = 0.045). Levels of Ang-1 showed a significant positive correlation with steroid dose. Patients who received cyclophosphamide or steroids showed a significant increase in plasma Ang-1 level. This was further confirmed by the results of the multivariate analysis. There was no significant association between plasma Ang-1 levels and other clinical manifestations or disease activity and severity. Plasma Ang-1 levels were diminished in our BD patients especially in patients with vascular involvement. Larger studies with further investigations of the precise role of Ang-1 in the pathogenesis of BD are needed and might lead to novel therapies for the clinical management of BD     

Studies of bronchoalveolar lavage cells and fluids in pulmonary sarcoidosis. I. Enhanced capacity of bronchoalveolar lavage cells from patients with pulmonary sarcoidosis to induce angiogenesis in vivo

Both allogeneic immunocompetent CD4+ lymphocytes and activated macrophages of mice can induce neovascularization when inoculated intradermally into host animals. Because sarcoidosis is associated with an increase in both activated macrophages and CD4+ effector lymphocytes in the lung, we carried out experiments in which cells obtained by bronchoalveolar lavage (BAL) of patients with pulmonary sarcoidosis were tested in a murine intradermal angiogenesis assay. BAL cells from patients with pulmonary sarcoidosis induced a significantly greater degree of angiogenesis than those from normal volunteers or from patients with other lung diseases. Moreover, the degree of angiogenesis induced by BAL cells from patients with sarcoidosis correlated positively with the severity of the disease. When BAL cells were separated into macrophage and lymphocyte subpopulations by flow cytometric techniques, the observed angiogenic activity was restricted primarily or exclusively to macrophages; lymphocytes were unable to induce angiogenesis in this xenogeneic assay system. These experiments suggest that pulmonary macrophages may play a role in the pathogenesis of sarcoidosis by inducing changes in the pulmonary microvasculature. Moreover, we hypothesize that these vascular changes may be induced not only in the lung but also in other organ systems such as skin, muscle, and eye in which microangiopathies are associated with sarcoid disease.     

Physical inactivity increases endostatin and osteopontin in patients with coronary artery disease

The balance between the angiostatic factor endostatin (ES) and angiogenic factor osteopontin (OPN) is essential in physiological and pathological angiogenesis. Several circumstances might influence this equilibrium and are of distinct interest when investigating mechanisms in coronary artery disease (CAD). The present explorative cross-sectional study was to investigate the influence of physical inactivity on ES and OPN levels in 181 male and 71 female patients with angiographycally verified CAD. Anamnestic and laboratory data were collected; ES was measured in serum and OPN in plasma by ELISA. Univariate analysis of variance was used to test for the influence of physical activity on ES and OPN levels and age, BMI, sex and diabetes status were included as covariates. ES and OPN intercorrelated significantly (r = 0.42; p < 0.001). ES and OPN decreased significantly in response to increasing activity level of patients suffering CAD (F = 5.5; p < 0.001 and F = 3.6; p < 0.01 resp.). This study is the first to show a linear decrease in ES and OPN levels in CAD patients depending on the degree of physical activity undergone. Lower levels of ES and OPN in physically active patients might be a sign of increased angiogenesis and decreased inflammation and calcifying activity and therefore contribute to the understanding of the damaging effect of physical inactivity in cardiovascular disease.     

Serum nerve grow factor and brain-derived neurotrophic factor profiles in Sjögren’s syndrome concomitant with interstitial lung disease

The aim of this study is to investigate the serum levels and clinical significance of nerve grow factor (NGF) and brain-derived neurotrophic factor (BDNF) in Sjogren’s syndrome (SS) with interstitial lung disease (ILD). Fifty two untreated patients with SS were enrolled in the study. Of them, 25 patients only displayed salivary glands damage and/or lacrimal gland injury (simple SS group). The other 27 patients were lacrimal and/or salivary gland involvement as well as being concomitant only with intestinal lung disease (ILD group). Twenty-five serum samples from healthy volunteers were examined as controls. We measure serum NGF and BDNF levels by ELISA and correlate them with clinical data. Serum NGF levels were significantly higher in ILD patients (372?±?129 pg/ml) and simple SS patients (293?±?72 pg/ml) when compared with healthy controls (187?±?47 pg/ml) (both p?<?0.01). Significant difference were also found between the two patient groups (p?<?0.01). In contrast, BDNF were significantly decreased in ILD patients (1,005?±?143 pg/ml) when compared with either simple SS patients (1,204?±?176 pg/ml, p?<?0.01) or healthy controls (1,217?±?155 pg/ml, p?<?0.01). Correlation analysis showed NGF levels in ILD patient were positively correlated with serum levels of C-reactive protein and IgG (both p?<?0.05). The abnormal NGF and BDNF in sera may be a potential character of ILD secondary to pSS.     

Pulmonary function in ankylosing spondylitis: association with clinical variables

To evaluate the association between pulmonary function and clinical variables in ankylosing spondylitis (AS) and to compare the pulmonary function of patients with AS with that of healthy controls, 61 AS patients and 74 healthy controls were included. In AS, we assessed clinical disease indices (BASDAI, BASFI, BASG), morning stiffness, number of hypersensitive entheses, metrology measures, 6-min walking test, acute phase reactants, radiological presence of “bamboo spine,” and severity of radiological involvement in sacroiliac and vertebral joints. AS and healthy controls had similar age and gender. All the parameters of pulmonary function were significantly diminished in AS than in healthy controls (p < 0.001), with a higher proportion of restrictive pattern (57.4 vs. 5.4 %). In AS, pulmonary function correlated negatively with BASDAI, BASFI, BASG, morning stiffness, number of hypersensitive entheses, occiput-wall distance, and ESR, and positively with 6-min walking test. There was no association between pulmonary function with radiological stage of vertebral joints and sacroiliac joints, “bamboo spine,” disease duration, or chest expansion. A higher frequency of AS patients had a decreased pulmonary function and results of the 6-min walking test. These abnormalities in AS were more related with disease activity than with mobility limitation.     

ACE deletion polymorphism is associated with a high risk of non-infectious pulmonary complications after stem cell transplantation

Non-infectious pulmonary complication (NIPC) is a serious adverse event for allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. NIPC includes both categories of lung complications: early onset idiopathic pneumonia syndrome (IPS) (onset <120 days) and late-onset non-infectious pulmonary complications (LONIPCs). Both categories have high mortality and morbidity rates, and critical treatments are not available. The renin–angiotensin system plays a critical role in pulmonary fibrosis. We, therefore, studied the relationship between angiotensin-converting enzyme gene (ACE) insertion/deletion polymorphisms and NIPC incidence in 149 consecutive allo-HSCT recipients. A total of 12.1 % (18/149) of these patients were diagnosed with NIPC (IPS, 3; LONIPCs, 15). Eight NIPC patients died from respiratory failure (mortality rate, 44.4 %). Peripheral blood stem cell transplantation was associated with a significantly higher incidence of NIPC than bone marrow transplantation and cord blood transplantation by univariate analysis (HR 3.13, P = 0.031). The serum ACE levels differed significantly according to the ACE insertion/deletion polymorphism. Patients with an ACE D/D genotype occurred at a significantly higher frequency among NIPC patients than I/D and I/I patients (HR 9.03, P < 0.0001). Multivariate analysis confirmed that NIPC is associated with ACE D/D genotypes (HR 8.8, P < 0.001). Our data support a role for the renin–angiotensin system in the pathogenesis of NIPC after allo-HSCT, and may represent a therapeutic target for complications.     

High circulating VEGF level predicts poor overall survival in lung cancer

Purpose

Vascular endothelial growth factor (VEGF) is considered as the best-validated key regulator of angiogenesis, while the prognostic role of circulating VEGF in lung cancer remains controversial. We conducted a meta-analysis to evaluate the prognostic role of circulating VEGF.

Methods

Nineteen studies with a total number of 2,890 patients were analyzed in our meta-analysis. Hazard ratios (HRs) and their 95 % confidence intervals (CIs) were used to quantify the predictive ability of circulating VEGF on survival.

Results

The pooled HR of all 17 studies evaluating overall survival (OS) was 1.29 (95 % CI 1.19–1.40, p < 0.001), indicating high circulating VEGF predicted poor OS. When grouped by disease stages, the pooled HRs were 0.97 (95 % CI 0.47–1.47, p < 0.001) for operable stage and 1.34 (95 % CI 1.18–1.49, p < 0.001) for inoperable stage. The pooled HRs were 1.28 (95 % CI 1.15–1.42, p < 0.001) for serum and 1.31 (95 % CI 1.13–1.49, p < 0.001) for plasma, when categorized by blood sample. Meta-analysis of circulating VEGF related to progression-free survival (PFS) was performed in 7 studies, and the pooled HR was 1.03 (95 % CI 0.96–1.09).

Conclusions

Our results indicate that high level of circulating VEGF predicts poor OS in lung cancer, yet it does not predict poor PFS.     

IL22 in Egyptian SLE patients,could it reflect disease activity,skin or renal involvement or is it only an expensive ESR?

Aim of the work

To analyze the level of interleukin 22 (IL-22) in sera of systemic lupus erythematosus (SLE) patients and to associate its level to disease activity, skin involvement and lupus nephritis.

Dynamics of serum angiopoietin-2 levels correlate with efficacy of intravenous pulse cyclophosphamide therapy for interstitial lung disease associated with systemic sclerosis

Objective

Angiopoietin-2 (Ang2) regulates the transition between vascular quiescence and angiogenesis in a context-dependent manner. In systemic sclerosis (SSc), serum Ang2 levels correlate with its disease activity. Therefore, we investigated the clinical significance of monitoring serum Ang2 levels during intravenous pulse cyclophosphamide (IVCY) therapy in SSc patients with interstitial lung disease (ILD).

Methods

Serum Ang2 levels were determined by a specific enzyme-linked immunosorbent assay in seven SSc patients treated with IVCY and 20 healthy controls. In the patient group, serum samples were drawn the day before each IVCY therapy.

Results

Serum Ang2 levels tended to be higher in SSc patients before IVCY than in healthy controls and significantly correlated with KL-6, surfactant protein D, erythrocyte sedimentation rate, and C-reactive protein in SSc patients with ILD. In sera drawn before the last IVCY, Ang2 levels were significantly decreased compared with initial levels. Notably, Δ serum Ang2 levels between baseline and after the first IVCY significantly correlated with Δ ILD score between before and after the entire IVCY therapy (r = 0.90, p < 0.01).

Conclusion

Monitoring Ang2 levels during IVCY treatment may be useful to evaluate and predict the efficacy of this treatment for SSc-ILD.     

Urinary interleukin 22 binding protein as a marker of lupus nephritis in Egyptian children with juvenile systemic lupus erythematosus

Juvenile systemic lupus erythematosus (JSLE) is a multi-system autoimmune inflammatory disease. Generally, 60% of patients will develop lupus nephritis (LN); thus, early recognition and treatment is associated with better outcome. Interleukin 22 (IL-22) is involved in tissue inflammation and is regulated by interleukin 22 binding protein (IL-22BP). This study aimed to use IL-22BP as a non-invasive marker for disease activity in JSLE and LN. This is a cross-sectional study conducted on 82 subjects: 51 JSLE patients and 31 healthy controls of matched age and gender. Urinary IL-22BP was measured using enzyme-linked immunosorbent assay, and its level was correlated with different clinical and laboratory data in JSLE as well as Systemic Lupus Erythematous Disease Activity Index 2000 (SLEDAI-2k), renal SLEDAI-2k, and Systemic Lupus International Collaborating Clinics (SLICC) renal activity score which were used to assess overall disease and renal activity. Our results showed that urinary IL-22BP level was significantly higher in JSLE patients with mean level of 4.13 ± 1.10, as compared to controls 1.63 ± 0.61 (P value < 0.001); also, patients with active LN had urinary levels of IL-22BP (5.47 ± 1.03) higher than patients with active JSLE without LN (4.23 ± 0.72) and patients with non-active JSLE/LN (3.5 ± 0.65) with a highly significant P value < 0.001. There was a positive correlation with SLEDAI-2k, renal SLEDAI, and renal activity scores (P < 0.001). Urinary IL-22BP may be used as a non-invasive marker for assessment of disease activity in children with JSLE and LN.     

Correlation between rapid-3, DAS28, CDAI and SDAI as a measure of disease activity in a cohort of Colombian patients with rheumatoid arthritis

The objective of this study is to correlate the patient-driven tool Routine Assessment of Patient Index Data 3 (RAPID-3) with other common tools used in daily practice to measure disease activity in rheumatoid arthritis (RA).One hundred nineteen RA patients according to 1987 American College of Rheumatology criteria who consecutively attended a RA outpatient clinic between August and December 2015 were evaluated. Data was stored in an electronic form that included demographic information, comorbidities, concomitant medication, and laboratory results. The disease activity was determined by tender and swollen joint count, pain and disease activity visual analog scales (VAS), disease activity score 28 (DAS28), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and multidimensional health assessment questionnaire (MDHAQ). Correlations between RAPID-3 and other disease activity tools were assessed. Mean age was 61 ± 13.8 years with a median disease duration of 14 years (IQR 5–21), 77% were females. Median scores were MDHAQ 0.5 (IQR 0.1–1.2), DAS 28 3.8 (IQR 2.7–5.1), and RAPID-3 12.3 (IQR 6–19). A strong correlation was obtained between RAPID-3 and DAS 28 (r 0.719, p < 0.001), CDAI (r 0.752, p < 0.001), and SDAI (r 0.758, p < 0.001). RAPID-3 had a high correlation with tools regularly used for disease activity assessment of RA patients in daily practice. The ease of its application favors routine use as it does not require laboratory results and joint counts.     

Modulation of peripheral immune responses by paclitaxel–ifosfamide–cisplatin chemotherapy in advanced non-small-cell lung cancer

Purpose

The aim of this study was to assess systemic immunological responses in non-small-cell lung cancer (NSCLC) patients with stage III/IV disease during treatment with paclitaxel–ifosfamide–cisplatin (TIP) chemotherapy.

Methods

Peripheral blood mononuclear cells (PBMCs) collected from healthy donors (HD) (n = 20) and chemotherapy-naive NSCLC patients treated with TIP (n = 32) were tested for production of IL-1, TNF-α, TNF-β, IL-6, IL-8, IL-10, IL-12 and IL-2 upon polyclonal stimulation with anti-CD3 mAb. They were further assessed over a treatment period of twelve weeks (i.e., four treatment cycles).

Results

PBMCs from NSCLC patients produced higher IL-1, TNF-α, TNF-β, IL-6, IL-8, IL-10 and IL-12 levels, whereas IL-2 exhibited lower values compared to HD (p < 0.001 for all parameters). Of interest, patients who responded to treatment had significantly higher increases in IL-2 (p < 0.001) and significantly higher decreases in IL-1 (p < 0.001), TNF-α (p < 0.001), TNF-β (p < 0.001), IL-6 (p = 0.02), IL-8 (p < 0.001), IL-10 (p < 0.001) and IL-12 (p < 0.001) levels. Non-responders revealed post-therapeutically a significantly higher increase in IL-1, TNF-α, TNF-β, IL-6, IL-8, IL-10 and IL-12 secretion and a significantly higher decrease in IL-2 levels (p < 0.001 for all parameters). Patients who responded to treatment and had a significantly higher increase in IL-2 showed a significantly longer median survival (p value < 0.001, 26 vs. 7.5 months).

Conclusion

Our study indicates that monitoring cytokine dynamics in patients with advanced NSCLC and especially those of IL-2 in peripheral blood components in vitro could be used as a predictor of treatment-related outcome and overall survival in NSCLC.     

Elevated serum levels of soluble CD146 in patients with systemic sclerosis

CD146, a transmembrane glycoprotein member of the immunoglobulin superfamily, acts as an adhesion molecule that helps maintain the cell monolayer. Human endothelial cells expressing CD146 are involved in angiogenesis and inflammation. Recently, we developed a sandwich ELISA for detecting soluble CD146 (sCD146) in human serum specimens. The aim of this study is to determine serum levels of sCD146 in patients with systemic sclerosis (SSc) and to examine the relationship between sCD146 levels and clinical manifestations. We quantified serum sCD146 levels in 47 serum samples from patients fulfilling criteria for SSc, 23 serum samples from patients fulfilling criteria for rheumatoid arthritis (RA), and 25 healthy controls. We also investigated the relationship between sCD146 levels and various clinical characteristics with SSc patients. Levels of sCD146 were significantly higher in the 47 patients with SSc than in the 25 healthy controls and 23 patients with RA (12.50 vs. 6.91 vs. 9.95 ng/ml; p < 0.001). Serum sCD146 levels in SSc patients with pulmonary arterial hypertension (PAH) were lower than in SSc patients without PAH (10.12 vs.13.17 ng/ml; p < 0.01). The serum levels of sCD146 were elevated in patients with SSc. However, decreased sCD146 levels were observed in SSc patients with PAH. Further studies are necessary to elucidate the sources and the mechanisms.     

Longitudinal assessment of monocyte chemoattractant protein-1 in lupus nephritis as a biomarker of disease activity

Urinary MCP-1 (uMCP-1) levels reflect lupus nephritis (LN) disease activity. However, long-term prospective studies evaluating it as a biomarker are lacking. SLE patients with active nephritis (AN), active disease without nephritis (ANR), and inactive disease (ID) were enrolled. AN patients were followed up every 3 months for 1 year. Urine and serum samples were collected at baseline from all and at follow-up visits in AN group. Urine samples from healthy subjects (HC), rheumatoid arthritis (RA), and diabetic nephropathy (DM) patients (20 each) served as controls. Serum (sMCP-1) and uMCP-1 was measured using ELISA. Urinary values were normalized for creatinine excretion. Nonparametric tests were used. A total of 121 SLE patients were enrolled. Baseline uMCP-1 was significantly higher in AN as compared to ANR, ID, HC, and RA (p < 0.001), but it was not different from DM and showed good correlation with rSLEDAI and SLEDAI (r = 0.52 and 0.47, p < 0.001) but not with sMCP-1. On ROC analysis to differentiate between AN and ANR, uMCP-1 performed better than sMCP-1, anti-dsDNA antibodies, C3 and C4. uMCP-1 and not sMCP-1 decreased significantly at all follow-up visits (p < 0.001). uMCP-1 remained persistently elevated in a patient who developed CKD and rose before conventional markers in two patients with relapse of LN. uMCP-1 correlates well with LN disease activity and helps differentiate between AN and ANR patients. Its levels fall with treatment and may have a potential to predict poor response and relapse of LN. uMCP-1 is most likely generated locally in the kidney.     

The Suppression Effects of Thalidomide on Human Lung Fibroblasts: Cell Proliferation, Vascular Endothelial Growth Factor Release, and Collagen Production

Background

Expression of transforming growth factor (TGF)-β₁ and increases in angiogenesis and deposition of extracellular matrix are the key features of tracheal granulation formation. The aim of this study was to investigate the potential role of thalidomide in preventing granulation tissue formation from the aspect of cellular effects in vitro, including fibroblast proliferation, vascular endothelial growth factor (VEGF) release, and collagen production.

Methods

Human lung fibroblasts were obtained from bronchus and cultured. The effects of thalidomide on cell proliferation, migration, TGF-β₁-induced VEGF, and signal pathway were investigated.

Results

Thalidomide (20 μM) not only inhibited cell proliferation after 24 h [fold increase of cell number, 0.85 ± 0.09 vs. 1.47 ± 0.14 (treatment vs. control group); P < 0.01] and 48 h of incubation (0.85 ± 0.10 vs. 1.97 ± 0.12; P < 0.001), it also inhibited cell migration and slowed wound closure at 24 h (P < 0.001). Thalidomide significantly attenuated TGF-β₁-induced VEGF expression at both the mRNA and protein levels. Incubation of thalidomide with cells stimulated with TGF-β₁ significantly inhibited their production of collagen. Thalidomide inhibited Smad3, STAT3, and subsequent p44/42 kinase phosphorylation.

Conclusion

Thalidomide may inhibit human fibroblast proliferation and it is worthy of further in vivo investigation.