Vasculitis and expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin in salivary glands of patients with Sjögren's syndrome

OBJECTIVE: We investigated the relationship between clinical symptoms and the grade of histopathological damage and expression of adhesion molecules in salivary glands of patients with Sj?gren's syndrome (SS). METHODS: We studied untreated and recently diagnosed patients with primary (n =20) and secondary SS [10 with SS and rheumatoid arthritis (RA); 10 with SS and systemic lupus erythematosus (SLE)] and 3 healthy controls. Salivary gland biopsies were performed in patients and controls and clinical data were obtained. Salivary gland biopsies were assessed for lymphocyte focus score and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. In serum, antinuclear antibodies, rheumatoid factor, anti-Ro and anti-La antibodies, anti-alpha-fodrin IgA and IgG antibodies, and gamma-globulin concentrations were measured. RESULTS: In salivary gland samples, ICAM-1 was expressed on vascular endothelial cells and lymphocyte foci, while VCAM-1 was expressed on vascular endothelial cells and follicular dendritic reticulin cells. There was a positive correlation between lymphocyte focus score and ICAM-1 expression (p < 0.05). We detected correlation between expression of ICAM-1 and VCAM-1, and the expression of VCAM-1 was significantly related to vasculitis (p < 0.05). The areas of E-selectin expression and the dispersion and severity of staining were not correlated with the focus score or with patients' clinical features (p > 0.05). There was no correlation between the staining and autoantibody positivity and gamma-globulin levels. CONCLUSION: ICAM-1 may be important for lymphocyte recruitment and glandular damage and VCAM-1 may be important for the development of vasculitis in patients with SS.     

Effects of interferon-α2a treatment on serum levels of tumor necrosis factor-α, tumor necrosis factor-α2 receptor, interleukin-2, interleukin-2 receptor, and E-selectin in Behçet's disease

This study was performed to investigate serum levels of various cytokines and E-selectin in patients with Behçet's disease (BD) before and after treatment with interferon-α2a (IFN-α). The study population consisted of 22 patients with active BD; 15 age- and sex-matched healthy adults served as the control group. IFN-α (3?million units subcutaneously) was given to all patients twice a week for 3?months. Twenty of twenty-two patients experienced clinical improvement with this therapy. Pre- and post-treatment serum levels of tumor necrosis factor-α (TNF-α), TNF-α2-receptor (TNFα2R), interleukin-2 (IL-2), IL-2 receptor (IL-2R), and E-selectin were measured by sandwich-type enzyme immunoassay. Baseline E-selectin, TNF-α, and TNF-α2R levels of the patients were increased in comparison with the control group and post-treatment values. However, IL-2 and IL-2R levels did not change either with treatment or compared with the control group levels. In conclusion, these results confirm the previously described efficacy of IFN-α in the treatment of BD. Serum levels of TNF-α, TNF-α2R, and E-selectin are prominently increased during active stage of the disease, indicating presence of immune system activation and endothelial injury/activation. Improvement of the pathological cytokinemia and endothelial disturbance accompany interferon-α-induced disease remission.     

Plasma tumor necrosis factor-α and C-reactive protein as biomarker for survival in head and neck squamous cell carcinoma

Purpose

Tumor TNM staging is the main basis for prognosis and treatment decision for head and neck squamous cell carcinoma (HNSCC) despite significant heterogeneity in terms of outcome among patients with the same clinical stage. In this study, a possible role of plasma interleukin-2 (IL-2), interleukin-6 (IL-6), granulocyte–macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) as biomarkers for survival of HNSCC patients was investigated.

Methods

In this prospective study, plasma levels of IL-2, IL-6, GM-CSF, TNF-α and CRP in patients (n = 100) and controls (n = 48) were analyzed.

Results

Significantly elevated levels of CRP and TNF-α (p < 0.001) were found in the patients. Combination of upregulated CRP and TNF-α in the patient plasma was significantly related to shorter patient survival, independent of clinical stage.

Conclusions

Our findings indicate that CRP and TNF-α might be suitable as biomarkers in combination with tumor TNM staging for predicting survival and individualized treatment of HNSCC patients. Plasma CRP and TNF-α analysis are simple, rapid, cost effective and suitable for clinical practice.     

Evaluation of preoperative and postoperative serum interleukin-6, interleukin-8, tumor necrosis factor α and raftlin levels in patients with obstructive sleep apnea

Background

Raftlin is a large, major lipid raft protein of cell membranes. Raftlin levels have not been previously examined in patients with obstructive sleep apnea (OSA). Our study aimed to evaluate the changes in raftlin, interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNFα) values from the preoperative state to the third month postoperatively in patients undergoing expansion sphincter pharyngoplasty for OSA.

Methods

Of 60 patients, 10 patients had mild OSA (AHI 5–14), 10 moderate (AHI 15–29), 10 severe (AHI ≥ 30), and 30 with AHI < 5 formed a control group. Preoperatively and at 3 months post-operatively, IL-6, IL-8, TNFα, and raftlin values were measured.

Results

Preoperatively, mean raftlin levels were 914.4 ± 62.7 pg/mL for controls, 910.0 ± 42.5 pg/mL in mild, 1000.5 ± 63.3 pg/mL in moderate, and 1386.3 ± 101.4 pg/mL in severe groups, with moderate and severe groups significantly elevated compared to controls (p < 0.001). Preoperatively to 3 months post-operatively, raftlin levels decreased significantly in each OSA group (p < 0.05). Levels of IL-6, IL-8 and TNFα followed similar patterns at baseline and after surgical intervention.

Conclusions

Raftlin levels at the third postoperative month decreased significantly compared with preoperative levels in parallel with other markers of inflammation.

     

Relative expression and correlation of tumor necrosis factor-α, interferon-γ, and interleukin-17 in the rheumatoid synovium

Although tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and interleukin-17 (IL-17) play important roles in RA, their relative expression and possible correlation in synovial tissues are not well understood. In this study, mRNA expression levels of IFN-γ, IL-17, and TNF-α were investigated in individual patients with RA and the correlations between pairs of these three pro-inflammatory cytokines were analyzed. Synovial tissues were obtained during arthroplasties from 24 joints of 24 RA patients. After harvesting synovial tissues, total RNA was isolated then quantitative real-time polymerase chain reaction (qRT-PCR) for IFN-γ, IL-17, and TNF-α was performed. Correlation of expression levels between them was also analyzed. Expression levels of TNF-α, IFN-γ, and IL-17 in patients receiving TNF inhibitors (TNFi) and those treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) alone were also compared between groups. Based on relative expression levels of the three pro-inflammatory cytokines, patients were classified into three major types; an IFN-γ plus TNF-α-dominant type, an IL-17-dominant type, and the other type. TNF-α expression levels were correlated with IFN-γ. In addition, there was a negative correlation between TNF-α and IL-17, and IFN-γ and IL-17. Median relative expression levels of TNF-α have no significant difference between the TNFi and the csDMARDs groups. In the rheumatoid synovial tissues, expression levels of TNF-α were modulated in parallel with IFN-γ, and TNF-α and IL-17, or IFN-γ and IL-17 did not co-express at high levels. This characteristic expression pattern of the three pro-inflammatory cytokines may be clinically useful information in the current cytokine-targeted treatment with biological DMARDs for RA.     

Serum macrophage inflammatory protein-lαand high-sensitivity C-reactive protein levels in the paitents with obstructive sleep apnea-hypopnea syndrome and hypertension

Objectives To identify the effects of obstructive sleep apnea-hypopnea syndromemacrophage inflammatory protein -1α(MIP-1α) and high-sensitivity c-reactive protein(hs-CRP) levels,and its impact on cardiac structure and function in patients with hypertension.(OSAHS) on serum. Methods We studied 86 middle-aged subjects classified into four groups according to the absence or presence of OSAHS with and without hypertension.(1)OSAHS patients without hypertension(OSAHS group,n=29);(2)OSAHS patients with hypertension(OSAHS +HT group,n=27);(3) non-OSAHS patients with hypertension(HT group,n =27);(4)volunteers without OSAHS and hypertension(Control subjects, n=27).OSAHS patients were divided into mild,moderate and severe degree based on apnea hypopnea index(AHI).All participants underwent polysomnography and echocardiography. Serum MIP-1αand hs-CRP levels were tested by enzyme linked immunosorbent assay(ELISA).Results Body mass index(BMI),neck collar(NC),waist-to-hip ratio(WHR) in OSAHS group and OSAHS +HT group were significantly higher than those in Control group(PP<0.05).Serum MIP- 1αlevels in OSAHS+HT group was significant higher than HT groups(P<0.05).Serum MlP-1αlevels in those three groups were negative correlationwith AV(r=-0.238,P=0.08) and positively correlated with E/A ratio(r=0.307,P=0.02). Conclusions We have not foundthe cardiac systolic function change in early OSAHS patients with hypertension,while the diastolic function decreased obviously.Serum MIP-1αlevel shows earlier change than hs-CRP level in OSAHS patients which may contribute to the lesion of cardiac diastolic function.     

Correction to: Evaluation of preoperative and postoperative serum interleukin-6, interleukin-8, tumor necrosis factor α and raftlin levels in patients with obstructive sleep apnea

Sleep and Breathing - A Correction to this paper has been published: https://doi.org/10.1007/s11325-021-02317-z     

Interleukin-6 and tumor necrosis factor-α are not increased in patients with Type 2 diabetes: evidence that plasma interleukin-6 is related to fat mass and not insulin responsiveness

Aims/hypothesis Our aim was to examine the possible direct relationship of interleukin-6 and TNF with insulin sensitivity in humans.Methods We carried out two series of euglycaemic-hyperinsulinaemic clamp experiments. In the first (CLAMP1), skeletal muscle mRNA expression and plasma concentrations of IL-6 and TNF were examined in patients with Type 2 diabetes (n=6), subjects matched for age (n=6), and young healthy (n=11) control subjects during a 120-min supra-physiological hyperinsulinaemic (40 mU·m^–2·min^–1) euglycaemic clamp. In the second series of experiments (CLAMP2), patients with Type 2 diabetes (n=6) and subjects matched for age (n=7) were studied during a 240-min high-physiological hyperinsulinaemic (7 mU·m^–2·min^–1) euglycaemic clamp, during which arterial and venous (femoral and subclavian) blood samples were measured for IL-6 and TNF flux.Results In both experiments the glucose infusion rate in the patients was markedly lower than that in the other groups. In CLAMP1, basal skeletal muscle IL-6 and TNF mRNA were the same in all groups. They were not affected by insulin and they were not related to the glucose infusion rate. In CLAMP2, neither cytokine was released from the arm or leg during insulin stimulation in either group. In both experiments plasma concentrations of these cytokines were similar in the patients and in the control subjects, although in CLAMP1 the young healthy control group had lower (p<0.05) plasma IL-6 concentrations. Using data from all subjects, a strong positive correlation (r=0.85; p<0.00001) was observed between basal plasma IL-6 and BMI. Conversely, a negative relationship (r=–0.345; p<0.05) was found between basal plasma TNF and BMI, although this was not significant when corrected for BMI. When corrected for BMI, no relationship was observed between either basal plasma IL-6 or TNF and GIR.Conclusions/interpretation These data show that the increased circulating IL-6 concentrations seen in patients with Type 2 diabetes are strongly related to fat mass and not insulin responsiveness, and suggest that neither IL-6 nor TNF are indicative of insulin resistance.Abbreviations CLAMP1 First series of experiments - CLAMP2 Second series of experiments - CON1 Healthy, sedentary, age- and BMI-matched control subjects in CLAMP1 - CON2 Healthy, sedentary, age- and BMI-matched control subjects in CLAMP2 - D1 Patients with Type 2 diabetes in CLAMP1 - D2 Patients with Type 2 diabetes in CLAMP2 - GIR Glucose infusion rates - YOUNG younger control subjects in CLAMP1     

Correlation of serum levels and gene expression of tumor necrosis factor-α-induced protein-8 like-2 with Parkinson disease severity

Different immune-mediated mechanisms involved in the pathogenesis of Parkinson disease (PD) as a neurodegenerative and inflammatory disease. According to our knowledge, there is no report evaluating Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2), a cytokine maintaining immune homeostasis, in PD. We analyzed the correlation of the serum levels and circulatory gene expression of TIPE2 with severity of PD. In this case-control study, 43 patients with PD and 40 healthy subjects were enrolled. The diagnosis of PD was performed byclinical diagnostic criteria of the UK Parkinson’s Disease Society Brain Bank. The severity of PD was evaluated by modified Hoehn and Yahr (H and Y) scale. Serum levels and gene expression of TIPE2 were assessed by Elisa and real time PCR, respectively. The mean serum levels and gene expression of TIPE2 in patients with PD did not have significant difference compared to healthy subjects. Linear multiple regression analysis showed that increased serum levels of TIPE2 are positively related to age and severity of PD (P?≤?0.0001). In addition, the gene expression of TIPE2 was found to be associated with age (P?<?0.0001). Our study showed that the serum levels of TIPE2 and its gene expression might be important prognostic biomarkers of PD.     

Role of cytokine gene (interferon-γ, transforming growth factor-β1, tumor necrosis factor-α, interleukin-6, and interleukin-10) polymorphisms in the risk of oral precancerous lesions in Taiwanese

Oral squamous cell carcinoma can be preceded by some benign oral lesions with malignant potential, including leukoplakia, erythroplakia, oral lichen planus, and oral submucous fibrosis. There are different degrees of inflammatory cells infiltration in histopathology. Inflammatory cytokines may play a pathogenic role in the development of oral precancerous lesions (OPCLs). Genetic polymorphisms of cytokine-encoding genes are known to predispose to malignant disease. We hypothesized that the risk of OPCLs might be associated with cytokine gene polymorphisms of interferon (IFN)-γ, transforming growth factor (TGF)-β1, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10. In the present study, 42 OPCL patients and 128 controls were analyzed for eight polymorphisms in five different cytokine genes [IFN-γ (+874 T/A), TGF-β1 (codons 10 T/C and 25 G/C), TNF-α (?308 G/A), IL-6 (?174 G/C), and IL-10 (?1082 A/G, –819 T/C, and ?592 A/C)]. Cytokine genotyping was determined by the polymerase chain reaction sequence-specific primer technique using commercial primers. Allele and genotype data were analyzed for significance of differences between cases and controls using the Chi-square (χ²) test. Two-sided p < 0.05 were considered to be statistically significant. A series of multivariate logistic regression models, adjusted for age, sex, betel quid chewing, alcohol consumption, and smoking, was constructed in order to access the contribution of homozygous or heterozygous variant genotypes of polymorphisms. The TNF-α (?308) polymorphism was significantly associated with OPCLs. There were significant differences in the distribution of AA, GA, and GG genotypes between OPCL patients and controls (p = 0.0004). Patients with the AA or GA genotype had a 3.63-fold increased risk of OPCLs. The TGF-β1 (codon 10 and 25) polymorphism was also significantly associated with OPCLs (p < 0.001). The IL-6 polymorphism was significantly associated with OPCLs. There are significant differences in the distribution of CC, GC, and GG genotypes between OPCL patients and controls (p < 0.001). Patients with the CC or GC genotype had a 35- or 20.59-fold increased risk of OPCLs. There were no significant differences in the distribution of IL-10 and IFN-γ genotypes between different groups of control individuals and OPCL patients. The IL-6, TGF-β1, and TNF-α gene polymorphisms may have a significant association with the development of OPCLs.     

Visceral fat decreased by long-term interdisciplinary lifestyle therapy correlated positively with interleukin-6 and tumor necrosis factor-α and negatively with adiponectin levels in obese adolescents

The purpose of this study was to assess the level of cytokine expression in correlation with visceral and subcutaneous fat in obese adolescents admitted to long-term interdisciplinary weight loss therapy. The study was a longitudinal clinical intervention of interdisciplinary therapy. Adolescents (18, aged 15-19 years) with body mass indexes greater than the 95th percentile were admitted and evaluated at baseline and again after 1 year of interdisciplinary therapy. Visceral and subcutaneous fat was analyzed by ultrasonography. Blood samples were collected to analyze tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and adiponectin concentrations that were measured by enzyme-linked immunosorbent assay. The most important finding in the present investigation is that the long-term interdisciplinary lifestyle therapy decreased visceral fat. Positive correlations between IL-6 levels and visceral fat (r = 0.42, P < .02) and TNF-α levels and visceral fat (r = 0.40, P < .05) were observed. Negative correlations between TNF-α levels and subcutaneous fat (r = −0.46, P < .01) and adiponectin levels and subcutaneous fat (r = −0.43, P < .03) were also observed. In addition, we found a positive correlation between TNF-α levels and the visceral to subcutaneous fat ratio (r = 0.42, P < .02) and a negative correlation between adiponectin level and the visceral to subcutaneous fat ratio (r = −0.69, P < .001). Despite the limitation of sample size, our results indicate that the observed massive weight loss (mainly visceral fat) was highly correlated with a decreased inflammatory state, suggesting that the interdisciplinary therapy was effective in decreasing inflammatory markers.     

C-reactive protein,procalcitonin,interleukin-6,vascular endothelial growth factor and oxidative metabolites in diagnosis of infection and staging in patients with gastric cancer

AIM:The current study was to determine the serum/pLasmalevels of VEGF,IL-6,malondialdehyde (MDA),nitric oxide(NO),PCT and CRP in gastric carcinoma and correlation withthe stages of the disease and accompanying infection.METHODS:We examined the levels of serum VEGF,IL-6,PCT,CRP and plasma MDA,NO in 42 preoperative gastriccancer patients and 23 healthy subjects.There were infectionanamneses that had no definite origin in 19 cancer patients.RESULTS:The VEGF levels (mean±SD; pg/mL) were478.05±178.29 and 473.85±131.24 in gastric cancer patientswith and without infection,respectively,and these valueswere not significantly different (P>0.05).The levels of VEGF,CRP,PCT,It-6,MDA and NO in cancer patients weresignificantly higher than those in healthy controls and thelevels of CRP,PCT,It-6,MDA and NO were statisticallyincreased in infection group when compared with non-infection group (P<0.001).CONCLUSION:Although serum VEGF concentrations wereincreased in gastric cancer,this increase might not be relatedto infection.CRP,PCT,IL-6,MDA and NO have obviousdrawbacks in the diagnosis of infections in cancer patients.These markers may not help to identify infections in theprimary evaluation of cancer patients and hence to avoidunnecessary antibiotic treatments as well as hospitalization.According to the results of this study,IL-6,MDA,NO andespecially VEGF can be used as useful parameters todiagnose and grade gastric cancer.     

Serum levels of interleukin 1-β, tumor necrosis factor-α, soluble interleukin 2 receptor and soluble CD8 in seronegative spondylarthropathies

Summary Seronegative spondylarthropathies are disorders with the same predisposing antigen, namely HLA B27, a class I molecule of the HLA system. The mechanisms of the different diseases are unknown, and there is no proof of immune system participation. We have investigated patients with spondylarthropathies in order to search for an immunological component in the pathophysiology of these disorders, by measuring the serum level of two inflammatory cytokines-IL1 and TNF-by a radioimmunological assay and the serum level of two soluble T cell activation markers-soluble IL2 receptor and soluble CD8-by an enzyme-linked immunosorbent assay. The choice of soluble CD8 can be explained by the strong link between HLA B27 and spondylarthropathies. Our series compared 24 patients to 24 healthy matched controls. A similar IL1 serum level was observed in both groups, while in the patients there was a nonsignificant increase in the TNF level, a significant decrease in the soluble IL2 receptor level and a significant increase in the soluble CD8 serum level. The normal or moderately increased serum IL1 and TNF levels in the disease group do not exclued a local role for these cytokines in the synovium or other inflammatory areas. However, we found a higher soluble CD8 serum level in the patient group. Most of these patients were in clinical excerbation of their disease. As the serum level of soluble CD8 is well correlated with T CD8 lymphocyte activation, our data suggest that this lymphocyte subset is stimulated and consequently probably involved in seronegative spondylarthropathies.