Inflammatory biomarkers responses after acute whole body vibration in fibromyalgia

The aims of this study were 1) to characterize the intensity of the vibration stimulation in women diagnosed with fibromyalgia (FM) compared to a control group of healthy women (HW) matched by age and anthropometric parameters, and 2) to investigate the effect of a single session of whole body vibration (WBV) on inflammatory responses. Levels of adipokines, soluble tumor necrosis factor receptors (sTNFr1, sTNFr2), and brain-derived neurotrophic factor (BDNF) were determined by enzyme-linked immunosorbent assay. Oxygen consumption (VO2) was estimated by a portable gas analysis system, heart rate (HR) was measured using a HR monitor, and perceived exertion (RPE) was evaluated using the Borg scale of perceived exertion. Acutely mild WBV increased VO2 and HR similarly in both groups. There was an interaction (disease vs vibration) in RPE (P=0.0078), showing a higher RPE in FM compared to HW at rest, which further increased in FM after acute WBV, whereas it remained unchanged in HW. In addition, there was an interaction (disease vs vibration) in plasma levels of adiponectin (P=0.0001), sTNFR1 (P=0.000001), sTNFR2 (P=0.0052), leptin (P=0.0007), resistin (P=0.0166), and BDNF (P=0.0179). In conclusion, a single acute session of mild and short WBV can improve the inflammatory status in patients with FM, reaching values close to those of matched HW at their basal status. The neuroendocrine mechanism seems to be an exercise-induced modulation towards greater adaptation to stress response in these patients.

Inflammation and oxidative stress in heart failure: effects of exercise intensity and duration

Although acute exercise is apparently pro-inflammatory and increases oxidative stress, it can promote the necessary stress stimulus to train chronic adaptations in patients with chronic heart failure (CHF). This study aimed to compare the effects of exercise intensity and duration on the inflammatory markers soluble tumor necrosis factor receptor (sTNFR1) and interleukin-6 (IL-6), and on oxidative stress [malondialdehyde (MDA) and antioxidant enzymes: catalase (CAT) and superoxide dismutase (SOD)] in individuals with CHF. Eighteen patients performed three exercise sessions: 30 min of moderate-intensity (M30) exercise, 30 min of low-intensity (L30) exercise, and 45 min of low-intensity (L45) exercise. Blood analysis was performed before exercise (baseline), immediately after each session (after), and 1 h after the end of each session (1h after). Thirty min of M30 exercise promoted a larger stressor stimulus, both pro-inflammatory and pro-oxidative, than that promoted by exercises L30 and L45. This was evidenced by increased sTNFR1 and MDA levels after exercise M30. In response to this stressor stimulus, 1 h after exercise, there was an increase in IL-6 and CAT levels, and a return of sTNFR1 to baseline levels. These findings suggest that compared with the duration of exercise, the exercise intensity was an important factor of physiologic adjustments.

Lack of association between TRAF1/C5 rs10818488 polymorphism and rheumatoid arthritis in Iranian population

Rheumatoid arthritis [RA] is a multifactorial disorder related to the inflammatory response system with debilitating and painful conditions. Both genetic and environmental factors, with unknown etiology, play important roles in this disease pathogenesis. Recently, TRAF1/C5 [Tumor Necrosis Factor Receptor-Associated Factor 1/Complement Component 5] polymorphism associated with increased risk for RA has been studied in different populations worldwide, and inconsistent results have been obtained, rs 10818488 allele is located on TRAF1/C5 intergenic region, and has been predicted to be functional. A total of 100 sex- and age-matched people including RA patients [n = 50] and healthy individuals [n = 50] from Iran have been entered in this study and genotyped for rs 10818488 [A/G] polymorphism, using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism [PCR-RFLP]. In our study, rs10818488 allele was not associated with risk for RA in Iranian population [p > 0.05, OR = 1.27, 95% CI = 0.72-2.23]. Results revealed that this allele might be population-specific and not to be associated with their corresponding gene pool. However, further analyses are required to clarify other RA-associated markers in our community

Soluble inflammatory markers as predictors of virological response in patients with chronic hepatitis C virus infection treated with interferon-α plus ribavirin

The host immune response plays an important role in viral clearance in patients who are chronically infected with hepatitis C virus (HCV) and are treated with interferon and ribavirin. Activation of the immune system involves the release of pro and anti-inflammatory molecules that can be measured in plasma samples. The present study aimed to evaluate the association between pretreatment plasma levels of chemokines and soluble tumor necrosis factor receptors (sTNF-R) and the virological response in treated patients with chronic hepatitis C infection. Forty-one chronically-infected HCV patients that were being treated with interferon-α (IFN-α) plus ribavirin were included in the study. Socio-demographic, clinical and laboratory data were collected and pretreatment plasma levels of chemokine CCL2, CCL3, CCL11, CCL24, chemokine CXCL9, CXCL10, sTNF-R1 and sTNF-R2 were measured. The virological response was assessed at treatment week 12, at the end of treatment and 24 weeks after treatment. Pretreatment CXCL10 levels were significantly higher in patients without an early virological response (EVR) or sustained virological response (SVR) compared to responders [512.9 pg/mL vs. 179.1 pg/mL (p = 0.011) and 289.9 pg/mL vs. 142.7 pg/mL (p = 0.045), respectively]. The accuracy of CXCL10 as a predictor of the absence of EVR and SVR was 0.79 [confidence interval (CI) 95 percent: 0.59-0.99] and 0.69 (CI 95 percent: 0.51-0.87), respectively. Pretreatment plasma levels of the other soluble inflammatory markers evaluated were not associated with a treatment response. Pretreatment CXCL10 levels were predictive of both EVR and SVR to IFN-α and ribavirin and may be useful in the evaluation of candidates for therapy.

Evaluation of serum cartilage oligomeric matrix protein [Comp], soluble tumour necrosis factor receptor-II[sTNF-RII] and interleukin-6 [IL-6] levels in relation to serum estradiol, functional and radiologic findings in postmenopausal females with knee joint osteoarthritis

To evaluate the possible relation between serum levels of cartilage oligomeric matrix protein COMP, sTNF-RII, IL-6 and estradiol in post-menopausal females with clinically and radiologically documented osteoarthritic changes in the knee joint. Twenty post-menopausal females [PMOA] -with clinically and radiologically documented knee joint osteoarthritis were compared to a control group of ten post-menopausal females [control group [I]] and ten pre-menopausal females [control group [2]] "who were clinically and radiologically free of knee joint osteoarthritis. To all the studied subjects, a complete clinical examination was performed, including body mass index calculation, as well as scoring .systems for functional assessment of joint. Plain X-ray of both knee joints was performed. Serum samples were obtained for analysis of urea, creatinine, uric acid, total calcium, inorganic phosphates, C-reactive protein, rheumatoid factor COMP, sTNF-fUI, IL-6, and estradiol levels. The mean serum estradiol values in the PMOA, and control group [I] were significantly lower than their corresponding value in control group [2], and slightly lower in the PMOA than control group [1]. The mean serum COMP value was slightly higher in the PMOA group than its corresponding value in control group [1], and both mean sera values were significantly higher than their corresponding mean value in control group [2]. The mean serum sTNF-RII value was significantly higher in the PMOA group than its corresponding values in control group [1] and control group [2]. As regards mean serum IL-6 value, it was significantly higher in control group [1] than its corresponding values in the both PMOA and control group [2]. Based on ROC curve analysis in PMOA and control group [1], both serum COMP and sTNF-RII yitld a diagnostic specificity of 90% each, while the diagnostic sensitivity was 45% and 50% respectively. By using the combined approach, we were able to increase the diagnostic sensitivity of serum COMP and sTNF-RII to 90% and 83% respectively. On the other hand, the receiver operating characteristics [ROC] curve analysis of the same parameters in PMOA and control group [2], revealed a diagnostic sensitivity of 100% for each of serum COMP and s TNF-PJI as well as a diagnostic specificity of 90% for serum COMP and 70% for sTNF-RII. The fact that radiographic evidence of OA usually appears in advanced stages of the disease led to the need of identifying possible serum biochemical markers that could reflect the joint tissue status. From the above mentioned results, it could be concluded that the combined measurement of serum levels of the biochemical markers COMP and sTNF-RII may be used in identifying osteoarthritis in post-menopausal females. Furthermore, menopausal state per-se could play a role in the limitation of the diagnostic sensitivity of either of the two parameters if one of both analytes was chosen alone for measurement

Interleukin-6 and soluble tumor necrosis factor receptor proteins in patients with nonthyroidal illness syndrome

The whole mark of the pathogenesis of the nonthyroidal illness [NTI] syndrome is a decreased activity of hepatic type I 5'-deiodinase resulting in decreased transformation of T4 to T3 and increased rT3 and T4/T3 ratio. Much interest is centered on the role of cytokines in the etiology of the NTI syndrome. In this work we assessed the relation between serum thyroid hormone changes in the NTI and activation of the cytokine network as reflected by the serum levels of IL-6 and soluble TNF alpha R proteins [sTNF alpha Rp[55] and sTNF alpha Rp[75]]. Forty patients of NTI with low serum T3 [<1.3 nmol/l] and high T4/T3 ratio [>56/1] and 18 normal controls were included in this study. The patients were divided into two groups according to the serum levels of T4 as follows: Group I: Included 24 patients with subnormal T3 [<1.3 nmol/l] and normal T4 [>75 nmoI/I] levels. Group U: Included 16 patients with subnormal T3 [<1.3 nmoI/I] and T4 [<75 nmol/l] serum levels. Serum T3, T4 and TSH were determined by radioimmunoassay, and FT3 was estimated by ultrafiltration. IL-6, sTNF alpha Rp[55] and sTNF alpha Rp[75] were determined by enzyme linked immunoassays. Significant decrease in T3, FT3, T4 and TSH serum levels and increase in T4/T3 ratio, IL-6, sTNF alpha Rp[55] and sTNF alpha Rp[75] in each of the 2 patient groups as compared to controls and in Group U as compared to Group I were obtained. Taking all patients together, T3 and FT3 were highly correlated with each other and were negatively correlated with IL-6 and sTNF alpha R proteins. A strong relation was observed between serum IL-6, sTNF alpha Rp[55] and sTNF alpha Rp[75]. IL-6 and sTNF alpha R proteins, the anti-inflammatory cytokines might be determinants of the horrn that occur in SES as a useful mechanism to counteract excessive catabolism, minimize protein wasting and save energy expenditure during illness, however, in patients who manifest low T4, a maladaptation that aggravates the underlying illness might warrant T3 supplementation, glucose-insulin potassium/T3, and other recently administered modalities of therapy

Study of serum osteoprotegrin [OPG], tumor necrosis factor-related apoptosis-inducing ligand [Trail] and fetuin-A in patients with chronic renal failure

Vascular and valvular calcifications are strong prognostic markers of cardiovascular disease mortality in chronic kidney disease [CKD] patients especially those on hemodialysis. It has been demonstrated that CKD patients with osteodystrophy have increased atherosclerosis and, more recently, increased coronary artery calcification. Was to evaluate the link between renal failure, atherosclerosis, vascular calcification and inflammation by determining the role of serum osteoprotegrin [OPG], tumor necrosis factor-related apoptosis-inducing ligand [TRAIL], and Fetuin A in the development of vascular calcification in patients with End stage renal failure disease [ESRD]. The study included, thirty patients on maintenance hemodialysis [HD] and fifteen patients with conservatively managed chronic renal failure [CRF] for whom dialysis was not performed. Both groups were compared to fifteen age and sex matched healthy individuals who constituted the control group. To all the subjects clinical examination, and 12 lead electro-cardiography were done. To all subjects the following investigations were performed: routine biochemical analysis, serum OPG, Fetuin A and plasma TRAIL Also serum parathyroid hormone [PTH], Calcium [total and ionized], phosphorus [Ph], and C- reactive protein [CRP] were measured. Finaly carotid ultra sonography of the pelvis and hand, and calculation of vascular calcification score were done. Carotid intima media thickness [CIMT] was found to be significantly higher in both undialyzed [CRF] patients and dialyzed [HD] patients when compared to controls [p<0.001 leach]. Also the difference between both groups of patients was statistically significant [p: 0.014]. Calcification score was found to be significantly higher in CRF and HD patients when compared to controls [p: 0.047 and < 0.001 respectively] Serum OPG level was significantly higher in both undialyzed CRF and dialyzed HD patients when compared to the control group [p: 0.041 and < 0.001 respectively].The level was also found to be significantly higher in the HD group when compared to CRF patients [p< 0.001]. Serum fetuin A level was found to be significantly lower in both CRF and HD patients when compared to the control group [p: 0.02, 0.05 respectively]. As regards TRAIL levels, no significant difference was found between the three studied groups. The level of the PTH was significantly higher in CRF undialyzed and HD patients when compared to control group [p: 0.021 and < 0.001 respectively]. CRP level was significantly higher in both patients groups when compared to controls [p< 0.001, 0.04 respectively].In the total patients group: there was a positive significant correlation between VC score and both PTH and AP. There was a positive significant correlation between OPG and [CIMT, Fetuin, AP and total Ca]. There was also a positive significant correlation between Fetuin A and both TRAIL and Albumin. By performing multiple logistic regression, only serum PTH was significant independent predictor of vascular calcification [p=0.006] and serum OPG was significant independent predictor of inflammation. [p=0.029]. The only parameter with significant ROC curve was PTH. It could be finally concluded that the increased level of OPG in CRF and HD patients might be a compensatory self defensive response against other factors that promote vascular calcification, or may possess potentially damaging properties, while the decreased level of Fetuin A reflects an inadequate response against the development of VC. Also the increase level of CRP denotes an ongoing inflammatory state and this causes down regulation of fetuin A which may represent the essential link between chronic inflammation and vascular calcification. PTH was found to be the best diagnostic marker of VC of all studied parameters, and was also the most independent predictor of VC, while OPG was the most independent predictor of inflammation

The Association of the Activation-Inducible Tumor Necrosis Factor Receptor and Ligand with Lumbar Disc Herniation

PURPOSE: Herniated nucleus pulposus fragments are recognized by the immune system as a foreign-body, which results in an autoimmune reaction. Human activation-inducible tumor necrosis factor receptor (AITR) and its ligand, AITRL, are important costimulatory molecules in the pathogenesis of autoimmune diseases. Despite the importance of these costimulatory molecules in autoimmune disease, their role in the autoimmune reaction to herniated disc fragments has yet to be explored. The purpose of the present study is to investigate whether the overexpression of AITR and AITRL might be associated with lumbar disc herniation. MATERIALS AND METHODS: The study population consisted of 20 symptomatic lumbar disc herniation patients. Ten macroscopically normal control discs were obtained from patients with spinal fractures managed with anterior procedures that involved a discectomy. Peripheral blood samples from both the study patients and controls were collected. The expression levels of AITR and AITRL were investigated by flow cytometric analysis, confocal laser scanning microscopy, immunohistochemistry and by reverse transcriptase-polymerase chain reaction (RT-PCR). The soluble AITR and AITRL serum levels were measured by an enzyme-linked immunosorbent assay. RESULTS: Flow cytometric analysis revealed significantly higher levels of both AITR and AITRL in the lumbar disc herniation patients than in the controls. The AITRL expression levels were also increased in patients with lumbar disc herniation, shown by using confocal laser scanning microscopy, immunohisto-chemistry, and RT-PCR. Finally, soluble AITR and AITRL were elevated in the patients with lumbar disc herniations. CONCLUSION: The AITR and AITRL are increased in both the herniated disc tissue and the peripheral blood of patients with lumbar disc herniation.

Triglyceride and high-density lipoprotein levels as markers of systemic lupus erythematosus activity and their association with TNF-alpha and TNF receptor

There are some clues that measurement of triglyceride [TG] and high-density lipoprotein [HDL] and their correlation with tumor necrosis factor alpha [TNF-alpha]. soluble TNF-alpha receptor type I and type 2 [sTNFR1, sTNFR2] in serum could be valuable in the assessment of disease activity of systemic lupus erythematosus [SLE] patients. In this cross-sectional study, fasting blood samples were obtained from 43 SLE patients fulfilling four or more of the American College of Rheumatology [ACR] 1997 revised classification criteria for SLE. Disease activity was determined by using the Systemic Lupus Erythematosus Disease Activity Index [SLEDAI]. TG and HDL obtained after overnight fasting were analyzed by routine chemistry. Levels of circulating TNF-alpha. sTNFR1, and sTNFR2 were determined by enzyme-linked immunosorbent assay. Triglyceride levels were associated with SLEDAI [r = 0.59. P<0.001]. TNF-alpha [r = 0.27. P<0.01], and with sTNFR1 [r = 0.54. P < 0.001]: on the contrary. HDL levels were negatively associated with SLEDAI [r = -0.29. P<0.007]. TNF-alpha [r = -0.27. P<0.01] and sTNFR1 [r = -0.35. P<0.001]. The correlation of TG and HDL with sTNFR2 were [r = 0.13. P> 0.23] and [r = -0.17. P> 0.1]. respectively. In multiple logistic regression models, the levels of TNF-alpha and HDL were omitted. Dyslipoproteinemia with high TG/low HDL levels correlates with disease activity in SLE. and enhanced activity In the TNF-alpha .sTNFR system. With results of this study and similar studies, serum levels of TG, HDL, TNF-alpha. sTNFR1, sTNFR2 are valuable markers for estimation of disease activity in SLE

Serum leptin concentrations in patients with liver cirrhosis due to hepatitis c infection and its correlation with soluble tumor necrosis factor receptor I levels

The aim of this work is to study the serum levels of leptin and sTNF-RI and study the correlation between these two factors in patients with liver cirrhosis due to HCV. The present study was performed on 80 individuals; 60 patients with liver cirrhosis due to HCV Infection and 20 normal age and sex matched subjects as a control group. Serum leptin and sTNF-RI levels were measured by ELI.SA. The results showed significantly elevated serum leptin. [the mean value +/- SD 8.8 +/- 4.0 ng/mL vs 4.4 +/- 2.69 ng/ml. p<0.001], and serum sTNF-RI[mean +/- SD 6.2 +/- 2.3 ng/mI vs 2.25 +/- 0.39 ng/mI, P<0.001] in cirrhotic patients versus controls. There was positive significant correlation between serum leptin and serum total bilirubin [p<0.05] and negative significant correlation with serum albumin, and total protein [p<0.01]. There was positive significant correlation between serum sTNF-RI and serum total bilirubin. direct bilirubin, AST and ALP [p<0.05] and negative significant correlation with serum albumin, total protein. A /G ratio [p<0.01] and BMI [p<0.05]. There was Positive significant correlation between serum sTNF-RI and serum leptin [r=0.62, P=0.001]. In conclusion, in patients with liver cirrhosis, there is increase in the serum level of leptin due to increased levels of some cytokines as sTNF-RI the increase in serum leptin leads to loss of appetite and malnutrition

Neutrophil CD11b expression, soluble tumor necrosis factor receptors and plasma interleukin 6 as markers of early neonatal sepsis

The value of neutrophil CD11b expression, soluble tumor necrosis factor receptors [sTNF-R] 55 and 75 and plasma interleukin-6 [IL-6] in early detection of neonatal infection was studied in 288 neonates. The studied newborns were classified into 4 group: group 0 [not infected], group 1 [possibly infected], group 2a [probably infected, culture-ve] and group 2b [culture +ve infection]. We looked for the optimal cutoff points of these parameters using the receiver operating characteristics [ROC] curve. The neutrophil CD11b expression by flowcytometry [FCM] was >100 median FU in all neonates with confirmed infection, >60 in all but one neonate of those with suspected infection, and <60 FU in non-infected group. A cutoff value of 60 FU or greater a 96% sensitivity, and a negative value of 99%. The sTNF-R 55 levels were significantly higher in the culture +ve group; 2a [median 7ng/ml], 2b [median 12ng/ml], and 1 [median 7ng/ml] than group 0 [median 3.9 ng/ml]. The sensitivity and specificity of a cutoff level of 6 ng/ml were 75% and 69% respectively. Similarly, sTNF-R 75 levels in groups 2a [median 11.2ng/ml], 2b [median 7 ng/ml], and 1 [median 10.6 ng/ml] than group 0 [median 7 ng/ml]. With a cutoff value of 9 ng/ml, sensitivity and specificity were 80% and 67% respectively The median levels of plasma IL-6 in groups 2a, 2b, 1, and 0 were 700 pg/ml, 260 pg/ml, 160 pg/ml, and 0 pg/ml respectively. A cutoff value of 100 pg/ml was 83.3% sensitive and 90.3% specific in diagnosing neonatal infection. For newborns sampled at birth or within the 1st postnatal hour, sensitivity was 100% and specificity 92.3%. This high sensitivity persisted until the 12th hour of life. On the other hand sensitivity of C- reactive protein [CRP] was low initially but improved with progress of infection. It is concluded that neutrophil CD11b is a promising test for ruling out early onset neonatal sepsis. If validated prospectively, such assay may reduce hospital stay and antibiotic use in newborns at risk of sepsis. High plasma IL-6 alone before 12th hour of life, and combined with high CRP thereafter, provides a useful maker for identifying the majority infected neonates. The sTNF-R seem less useful in this context because of their smaller magnitude of variation

Serum concentrations of soluble 4-1BB and 4-1BB ligand correlated with the disease severity in rheumatoid arthritis

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease whose etiopathogenesis is not well understood. Although soluble (s) forms of 4-1BB (s4-1BB) and 4-1BB legand (s4-1BBL) have been detected in the sera of RA patients, their significance is not known. We compared the serum levels of s4-1BB and s4-1BBL in RA patients with those in systemic lupus erythematosus (SLE) and Behcet's disease (BD) patients. Serum levels of s4-1BB and s4-1BBL were significantly higher in RA patients compared with healthy controls, SLE or BD patients, and the abundance was correlated with disease severity in patients with RA. The serum levels of s4-1BB in RA patients were inversely corroborated with 4-1BB expression levels on activated T lymphocytes. In addition, there was a correlation between serum levels of s4-1BB and s4-1BBL. The augmented secretion of s4-1BB and s4-1BBL levels into the serum may reflect the clinical symptoms of RA and levels of s4-1BB and s4-1BBL in sera at the time of diagnosis may be indicative of the severity and outcome of RA.

Circulating tumour necrosis factor alpha & soluble TNF receptors in patients with Guillain-Barre syndrome.

BACKGROUND & OBJECTIVES: Tumour necrosis factor-alpha (TNF-alpha) is regarded as one of the immune factors that can induce demyelination of peripheral nerves in patients with Guillian-Barre syndrome (GBS). This present study was undertaken to find out the role of TNF-alpha and soluble TNF receptors in the pathogenesis of GBS; and to study the effect of intravenous immunoglobulin (ivIg) therapy on the serum TNF-alpha and soluble TNF receptors in patients with GBS. METHODS: Thirty six patients with GBS in progressive stages of motor weakness were included in this study. The serum TNF-alpha and soluble TNF receptors (TNF-RI, TNF-RII) were measured in the serum samples of these patients before and after ivIg therapy by a sandwich ELISA. RESULTS: Of the 36 patients with GBS, 26 (72.2%) showed elevated serum TNF-alpha levels prior to ivIg therapy. Following a complete course of ivIg therapy there was a progressive decrease in the serum TNF-alpha concentrations in these 26 patients. On the other hand, the soluble TNF receptors, particularly TNF-RII showed an increase in the serum of GBS patients following ivIg therapy. INTERPRETATION & CONCLUSION: The results indicate that ivIg reduces the serum TNF-alpha concentrations in the GBS patients having elevated levels prior to ivIg therapy. Elevated serum levels of soluble TNF receptors following ivIg therapy may play a protective role by inhibiting the demyelinating effect of TNF-alpha in the peripheral nerves of patients with GBS.

High levels of soluble herpes virus entry mediator in sera of patients with allergic and autoimmune diseases

Herpes virus entry mediator (HVEM) is a newly discovered member of the tumor necrosis factor receptor (TNFR) superfamily that has a role in herpes simplex virus entry, in T cell activation and in tumor immunity. We generated mAb against HVEM and detected soluble HVEM (SHVEM) in the sera of patients with various autoimmune diseases. HVEM was constitutively expressed on CD4(+)and CD8(+)T cells, CD19(+)B cells, CD14(+)monocytes, neutrophils and dendritic cells. In three-way MLR, mAb 122 and 139 were agonists and mAb 108 had blocking activity. An ELISA was developed to detect sHVEM in patient sera. sHVEM levels were elevated in sera of patients with allergic asthma, atopic dermatitis and rheumatoid arthritis. The mAbs discussed here may be useful for studies of the role of HVEM in immune responses. Detection of soluble HVEM might have diagnostic and prognostic value in certain immunological disorders.

The Origin of Proinflammatory Cytokines in Patients with Idiopathic Dilated Cardiomyopathy

Proinflammatory cytokines and their receptors are increased in the peripheral blood of patients with heart failure. We measured cytokines and their receptors in systemic artery (SA), coronary sinus (CS) and infra-renal inferior vena cava (IVC), in order to investigate their origin and influential factors. Thirty patients with idiopathic dilated cardiomyopathy were performed echocardiography at admission, and right heart catheterization after stabilization. Blood was drawn from 3 sites for measurement of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and soluble tumor necrosis factor- receptor (sTNFR) I, II. TNF-alpha at CS (3.25+/-0.34 pg/mL) was higher than those of SA (1.81+/-0.39 pg/mL) and IVC (1.88+/-0.38 pg/mL, p<0.05). IL-6 at CS (18.3+/-3.8 pg/mL) was higher than that of SA (5.8+/-1.2 pg/mL, p<0.01). The levels of sTNFR I, II showed increasing tendency in sequence of SA, IVC and CS. TNF-alpha and sTNFR I, II from all sites were proportional to worsening of functional classes at admission (p<0.05). E/Ea by Doppler study at admission, which reflects left ventricular end-diastolic pressure (LVEDP) was positively correlated with TNF-alpha from SA (R=0.71, p<0.01), CS (R=0.52, p<0.05) and IVC (R=0.46, p<0.05). Thus, elevated LVEDP during decompensation might cause cytokine release from myocardium in patients with idiopathic dilated cardiomyopathy.

Determination of soluble ICAM-1 and TNFalphaR in the cerebrospinal fluid and serum levels in a population of Brazilian patients with relapsing-remitting multiple sclerosis

Cytokines and adhesion molecules have been implicated in the pathogenesis of multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system. In this study we analyzed intrathecal (CSF) and serum levels of soluble intercellular adhesion molecule (ICAM-1) and TNFalphaR (60kD) from 20 patients with clinically definite MS during acute relapse or stable disease. Comparing to control groups of healthy individuals and patients with intervertebral herniated disc, MS patients showed increased levels (p< 0.001) of sICAM-1 and TNFalphaR in both serum and CSF samples. Regardless stage of disease there was no significant difference in the levels of sICAM-1 during acute relapse (657 + or - 124.9 ng/ml) or remission (627 + or - 36.2 ng/ml). A steady increase of TNFalphaR (60kD) in both serum and CSF, indicate the existence of a continuous inflammatory process within the brain tissue of MS patients despite absence of clinical signs of disease activity

Detection of circulant tumor necrosis factor-alpha, soluble tumor necrosis factor p75 and interferon-gamma in Brazilian patients with dengue fever and dengue hemorrhagic fever

Pro-inflammatory cytokines are believed to play an important role in the pathogenesis of dengue infection. This study reports cytokine levels in a total of 54 patients examined in Recife, State of Pernambuco, Brazil. Five out of eight patients who had hemorrhagic manifestations presented tumor necrosis factor-alpha (TNF-alpha) levels in sera which were statistically higher than those recorded for controls. In contrast, only one out of 16 patients with mild manifestations had elevated TNF-alpha levels. The levels of interleukin-6 (IL), IL-1beta tested in 24 samples and IL-12 in 30 samples were not significantly increased. Interferon-g was present in 10 out of 30 patients with dengue. The data support the concept that the increased level of TNF-alpha is related to the severity of the disease. Soluble TNF receptor p75 was found in most patients but it is unlikely to be related to severity since it was found with an equivalent frequency and levels in 15 patients with dengue fever and another 15 with dengue hemorrhagic fever

Circulating soluble tumour necrosis factor receptors in rheumatoid arthritis

Two types of tumur necrosis factor receptors, TNF-RI and TNF-RII, have been identified. It has been suggested that levels of soluble TNF receptors in the serum can serve as markers of disease activity in rheumatoid arthritis [RA]. This work was designed to measure the soluble TNF-RI and RII in serum of RA patients during disease activity and to find out if their levels reflect clinical response in these patients after methotrexate therapy for 24 weeks. This study was conducted on 30 patients with active RA and 16 healthy controls. The soluble TNF receptors were assayed before and after methotrexate therapy using ELISA technique. Our study revealed that the concentrations of soluble TNF-RI [P55] and RII [P75] were significantly higher in RA patients during disease activity compared to healthy controls [P<0.001 for each receptor]. After methotrexate therapy, a significant decrease in P55 sTNF-R concentration was associated with clinical improvement [P<0.001] while the decrease in P75 sTNFR concentration was found to be insignificant. We conclude that sTNF receptors [P55 and P75] serve as markers of disease activity in RA and we can consider P55 sTNF- R as a marker of clinical response and drug efficacy

Soluble interleukin-2 receptor [sIL-2R], tumor necrosis factor alpha [TNF - alpha] and its receptor as prognostic markers in non-hodgkin's lymphoma

This study aimed at assessing whether pretreatment levels of interleukin-6 [IL-6], interleukin-10 [IL-10], tumor necrosis factor-alpha [TNF- alpha], soluble TNF type 1 receptor [p55-R-TNF] and soluble interleukin-2 receptor [sIL-2R] are related to known clinical and biological prognostic factors of lymphoma. Thirty-five patients diagnosed to have non-Hodgkin's lymphoma [NHL] were studied. Patients were treated by 6 cycles of multiagent chemotherapy regimen containing Cyclophosphamide, Adriamycin, Vincristine and Prednisolone [CHOP]. Serum cytokines levels were determined in their serum by an Enzyme Amplified Sensitivity Immunoassay [EASIA] and chemiluminescent enzyme immunometric assay. Statistically significant higher pretreatment levels of sIL-2R [p<0.0001], IL-6 [P<0.0001], IL-10 [p=0.01] and p55-R-TNF [P<0.0001] were observed in NHL patients as compared to controls. sIL- 2R and TNF- alpha levels correlated with tumor burden [P> 0.02 and> 0.01, respectively], while, significantly high levels of IL-6, TNF- alpha and p55-R-TNF were found in patients presented with beta symptoms [P = 0.01, 0.05 and 0.025 respectively]. Following treatment, cytokine levels progressively declined in responding patients. However, no single parameter was found to be of independent prognostic significance. Dramatic variations in sIL- 2 R and TNF- alpha levels between responder and non-responders suggested that combination of these markers might have a prognostic value in management of NHL. These markers could be used in monitoring disease activity and identification of high risk patients who need more aggressive therapy