Soluble Receptor Concentrations Research Articles

Alarmins and Related Molecules in Elective Surgery

Surgery is associated with alterations of alarmins’ and related molecules’ levels. The aim of this study was to investigate which biomarkers are most involved in surgery. The studied group consisted of 58 patients with inguinal or umbilical hernia or cholecystolithiasis and 21 healthy controls for compa­rison. We also added seven acute patients with appendicitis, cholecystitis and incarcerated hernia. Serum concentrations of soluble receptor of advanced glycation end-products (sRAGE), extracellular newly identified receptor for advanced glycation end-products binding protein (EN-RAGE), calprotectin, high mobility group box 1 (HMGB1) and interleukin 6 (IL-6) were analysed by ELISA before and after surgery. Preoperative concentrations of calprotectin were significantly decreased while concentrations of sRAGE were significantly increased in patients compared to controls; the concentrations of EN-RAGE and HMGB1 did not differ significantly. IL-6 levels were undetectable in elective patients preoperatively and in controls. Postoperatively, there was a significant increase of EN-RAGE, calprotectin, HMGB1, and IL-6 and a significant decrease of sRAGE compared to preoperative levels. In acute patients, all tested molecules except for sRAGE were significantly increased preoperatively, and sRAGE was significantly decreased. In contrast, after surgery, we could observe a further increase in IL-6; the other biomarkers did not differ significantly. We can conclude that the concentrations of all tested biomarkers are significantly influenced by elective surgery. The postoperative levels of all tested molecules increase except for sRAGE, whose level is significantly decreased after surgery. In acute states, these molecules are already increased, and the influence of surgery is, apart from IL-6, insignificant.

How Diabetes and Other Comorbidities of Elderly Patients and Their Treatment Influence Levels of Glycation Products.

Medical care for geriatric patients is a great challenge, mainly due to various overlapping deficits relevant to numerous coexisting diseases, of which the most common are diabetes mellitus and atherosclerosis. In the case of diabetes, the glycation process is intensified, which accelerates atherosclerosis development and diabetic complications. Our goal was to investigate the relationship between the classical biochemical parameters of diabetes and atherosclerosis, as well as parameters which may indicate a nephropathy, and the parameters strictly related to glycation, taking into account the pharmacological treatment of patients. Methods: We analyzed the patients’ serum concentrations of fluorescent glycation product—pentosidine, concentrations of soluble receptors for advanced glycation products (sRAGE), lipoprotein receptor-1 (LOX-1), galectin 3 (GAL3), scavenger receptor class A (SR-A), and scavenger receptor class B (SR-BI), as well as the level of lipid peroxidation and free amine content. Among the identified correlations, the most interesting are the following: sRAGE with triglycerides (r = 0.47, p = 0.009), sRAGE with SR-BI (r = 0.47, p = 0.013), SR-BI with LOX-1 (r = 0.31, p = 0.013), and SR-BI with HDL (r = −0.30, p = 0.02). It has been shown that pentosidine and reactive free amine contents are significantly higher in elderly patients with ischemic heart disease. Pentosidine is also significantly higher in patients with arterial hypertension. Malondialdehyde turned out to be higher in patients with diabetes mellitus type 2 that was not treated with insulin or metformin than in those treated with both medications (p = 0.052). GAL3 was found to be lower both in persons without diabetes and in diabetics treated with metformin (p = 0.005). LOX-1 was higher in diabetic patients not treated with metformin or insulin, and lowest in diabetics treated with both insulin and metformin, with the effect of metformin reducing LOX-1 levels (p = 0.039). Our results were the basis for a discussion about the diagnostic value in the clinical practice of LOX-1 and GAL3 in geriatric patients with diabetes and also provide grounds for inferring the therapeutic benefits of insulin and metformin treatment.

High-Altitude Hypoxia Decreases Plasma Erythropoietin Soluble Receptor Concentration in Lowlanders.

Background: The soluble form of the erythropoietin (Epo) receptor (sEpoR) is an endogenous antagonist of Epo. Decreasing plasma sEpoR increases free Epo, thereby increasing the availability of the hormone. In humans, short-term intermittent normobaric hypoxia exposure reduces sEpoR concentration in plasma. However, whether similar changes occur during continuous hypoxia, such as during high-altitude exposure with ongoing acclimatization, is yet unknown. Therefore, this study aimed to characterize the time-course concentration profile of sEpoR, and also of Epo, reticulocyte count (RC), and hematocrit in healthy lowlanders during 4 days at high altitude.Methods: Twenty-two men residents at sea level traveled by road (∼7 hours) from Lima to Cerro de Pasco (4340 m) for 72 hours. Oxygen saturation as measured by pulse oximetry (SpO2), heart rate, systolic and diastolic blood pressure, Lake Louise Score, sEpoR, Epo, RC, and hematocrit were evaluated every 12 hours, starting 12 hours before the ascent.Results: Plasma sEpoR decreased by 19% and remained below baseline values throughout high-altitude exposure. In parallel, Epo levels increased during the first hours, reaching a peak at 48 hours, and then progressively decreased until 72 hours. As a result, the Epo-to-sEpoR ratio (Epo/sEpoR) remained significantly elevated compared with baseline values. RC increased linearly until the end of the protocol, and hematocrit only showed a marginal increase.Conclusion: Our results show that high-altitude hypoxia causes a significant and stable reduction of plasma sEpoR concentration within the first 24 hours, whereas plasma Epo constantly decreases after having reached a maximum by 48 hours. This simultaneous change leads to a relatively high Epo/sEpoR after 72 hours at high altitude. The early increase in hematocrit likely relates to hemoconcentration, but the steady increase in RC reflects a sustained erythropoietic drive that will lead to elevate hematocrit to a new steady state after acclimatization.

Methotrexate use, not interleukin 33, is associated with lower carotid intima-media thickness in patients with rheumatoid arthritis

BackgroundRheumatoid arthritis is a risk factor for early mortality due to cardiovascular disease. Interleukin-33 appears to protect against the development of atherosclerosis. The purpose of this study was to investigate the relationship between serum levels of interleukin-33 and its soluble receptor with the presence of subclinical carotid atherosclerosis in rheumatoid arthritis patients.MethodsRheumatoid arthritis patients without atherosclerotic disease were subjected to clinical and laboratory assessments, including carotid ultrasound. Interleukin-33 and its soluble receptor serum levels were measured by ELISA.Results102 patients were included. The prevalence of carotid plaques was 23.5% and the median intima-media thickness was 0.7 mm. The median interleukin-33 and its soluble receptor concentration was 69.1 and 469.8 pg/ml. No association was found between serum interleukin-33 or its soluble receptor and intima-media thickness or plaque occurrence. Each 0.1 mm increase of intima-media thickness raised the odds of plaque occurrence by 5.3-fold, and each additional year of rheumatoid arthritis duration increased the odds of plaque occurrence by 6%. Each additional year in patients age and each one-point increase in the Framingham Risk Score were associated with a 0.004 mm and 0.012 mm increase in intima-media thickness. Methotrexate use was associated with a 0.07 mm reduction in intima-media thickness.ConclusionsInterleukin-33 and its soluble receptor were not associated with subclinical atherosclerosis. Traditional risk factors for atherosclerosis and rheumatoid arthritis duration were associated with intima-media thickness and plaque occurrence; methotrexate use was associated with a lower intima-media thickness.

Positive effect of ozonotherapy on serum concentration of soluble interleukin-2 receptor and neopterin in patients with systemic sclerosis.

IntroductionSystemic sclerosis (SSc) is a chronic systemic autoimmune disease of unknown aetiology. No curative therapy exists, thus management includes controlling of symptoms and prevention of complications. Ozonotherapy has multiple beneficial therapeutic effects which can translate into improving prognostic factors for SSc.AimTo evaluate the effect of ozone on selected factors of inflammation: serum concentration of the soluble receptor of interleukin-2 (IL-2 sR), neopterin as well as the peripheral blood smear in patients with SSc.Material and methodsForty-two patients with SSc underwent two series of 10-minute baths in water with a mixture of air and ozone separated by a 10-day period without treatment. Examinations were performed at baseline and 10 days after completing the last treatment.ResultsThe mean concentration of IL-2 sR decreased significantly from 1563.73 to 1249.86 pg/ml. The mean concentration of neopterin decreased significantly from 12.06 to 10.9 nmol/ml. Absolute monocytosis decreased insignificantly from 1.694 to 1.480 G/l. Correlations between the disease duration and concentration of IL-2 sR were weak and negative, while between the disease duration and concentration of neopterin were weak and positive.ConclusionsOzonotherapy had a beneficial influence on the immune response in patients with scleroderma. Balneotherapy may be considered as an additional therapeutic option, but further research is required.

The volume of liver irradiated during modern free-breathing breast radiotherapy: Implications for theory and practice

IntroductionIncidental liver irradiation during breast radiotherapy can increase the risk of second primary malignancy and induce adverse inflammatory states. This study establishes the volume of liver irradiated during free-breathing breast radiotherapy. Novel associations between liver dose-volume data and systemic interleukin-6 soluble receptor and blood counts are evaluated. MethodsThe volume of liver within the 10%, 50% and 90% isodose was determined for 100 women with stage 0 to II breast carcinoma undergoing 40Gy in 15 fractions over three weeks tangential irradiation. Blood counts and interleukin 6 soluble receptor concentration were recorded before, during and four weeks after radiotherapy. Dose-volume data for right-sided treatments was associated with longitudinal measures at bivariate and multivariable levels. ResultsA maximum of 226cm3 (19%), 92 cm3 (8%) and 62 cm3 (5%) of the liver was irradiated within the 10%, 50% and 90% isodose. Liver irradiation was almost exclusively a feature of the 52 right-sided treatments and was strongly correlated with breast volume (ρ = 0.7, p < 0.0001). Liver V10% was significantly associated with interleukin-6 soluble receptor concentration four weeks post-radiotherapy (beta = 0.38, p = 0.01) after controlling for theoretical confounding variables. ConclusionUp to 8% of the liver is irradiated within the primary beam during local right-sided breast radiotherapy. Select use of a deep inspiration breath hold technique would reduce this volume, and minimise the risk of radiation-induced malignancy and acute systemic elevation of inflammatory interleukin 6 soluble receptor.

Influence of visceral obesity on the secretion of adipokines with epicardial adipocytes in patients with coronary heart disease

Aim. To study adipokine-cytokine profile of epicardial adipocytes (EAT) and subcutaneous adipose tissue (SAT) in conjunction with the area of visceral adipose tissue (VAT), biochemical and clinical characteristics of patients with coronary heart disease. Materials and methods. Examined 84 patients (70 men and 14 women) with coronary artery disease. In fact the presence of visceral obesity (VO) the patients were divided into two groups. Patients VO the sampling of adipocytes of EAT and SAT, with subsequent cultivation and evaluation of adipokine and provospalitelna activity. Carried out the determination of carbohydrate and lipid metabolism, adipokine and pro-inflammatory status in the blood serum. Results and discussion. It was found that adipokine-cytokine profile of adipocytes of EAT and SAT differ. Adipocytes art of the disease on the background characterized by an increase IL-1, TNF-α, leptin-adiponectin relationships and a decrease in the content of protective factors: adiponectin and anti-inflammatory cytokine IL-10. While the SAT adipocytes was characterized by a decrease in the concentration of soluble receptor for leptin and the more pronounced leptinresistance, and the increase in proinflammatory cytokines was offset by the increase in the concentration of IL-10. The presence associated with multi-vessel coronary bed lesion, multifocal atherosclerosis, insulin resistance, atherogenic dyslipidemia, an imbalance of adipokines and markers of inflammation. So the value of the square VAT determined higher concentrations of leptin, TNF-α in adipocytes and serum, lipid and carbohydrate metabolism and a lower content of soluble receptor for leptin. Conclusion. Thus, the disease on the background of the status of the adipocytes of EAT characterized as a "metabolic inflammation", and may indicate the direct involvement of adipocytes in the pathogenesis of coronary artery disease, due to the formation of adipokine imbalance and the activation of proinflammatory reactions.

Treatment Effects upon Prolactin and Soluble Receptor of Interleukin-2 in Psoriatic Patients

Psoriasis vulgaris is a chronic inflammatory hyper-proliferative disease of the skin, scalp, nails, and joints. It has been hypothesized that prolactin (PRL) may modulate the skin immune system and be involved in the pathogenesis of psoriasis. Psoriasis exerts significant, negative impact on patients' quality of life. Relatively high rates of depression are reported in patients with psoriasis. The aim of this work was to study the possible role of PRL in the pathogenesis of psoriasis and its correlation with the disease activity, clinically, molecular and emotional status of patients. A total of 41 samples were analyzed - 21 new patients with psoriasis vulgaris before treatment and 20 after therapy - were included in this study. In all patients, we determined skin disease activity according to the PASI index, the psychological impact measured with HAMA and HAMD scales and the quality of their life measured by DLQI. The concentration of prolactin in the serum was measured by enzyme-linked immunosorbent assay (ELISA), and the concentration of soluble receptor of IL-2 was measured with automated immune chemiluminescent system - IMMULITE procedure. The PRL and sIL2R serum levels were significantly decreased after three months of therapy, at least 50% with a p value <0.00001. Clinical, hormonal, molecular correlations between before and after therapy were measured with a statistically significant result. Correlations between HAMA-PRL and DLQI-PRL before therapy were not statistically significant, only the relationship between HAMD and PRL was demonstrated. After treatment, we obtained a significant clinical, psychological and paraclinical (especially serum levels of prolactin and sIL2R) decreased and relevant response on all the patients treated and analyzed. Prolactin seems to have a role in the pathogenesis of psoriasis and may represent a cause and/or a consequence of psoriasis pathology. The most likely scenario is that PRL enhances interferon-induced chemokine production in keratinocytes, thereby facilitating cutaneous T-cell infiltration. This raises the intriguing light that PRL may offer a novel future therapeutic target in psoriasis and other skin diseases that worsen in response to psychological distress.

Influence of visceral obesity on the secretion of adipokines with epicardial adipocytes in patients with coronary heart disease.

To study adipokine-cytokine profile of epicardial adipocytes (EAT) and subcutaneous adipose tissue (SAT) in conjunction with the area of visceral adipose tissue (VAT), biochemical and clinical characteristics of patients with coronary heart disease. Examined 84 patients (70 men and 14 women) with coronary artery disease. In fact the presence of visceral obesity (VO) the patients were divided into two groups. Patients VO the sampling of adipocytes of EAT and SAT, with subsequent cultivation and evaluation of adipokine and provospalitelna activity. Carried out the determination of carbohydrate and lipid metabolism, adipokine and pro-inflammatory status in the blood serum. It was found that adipokine-cytokine profile of adipocytes of EAT and SAT differ. Adipocytes art of the disease on the background characterized by an increase IL-1, TNF-α, leptin-adiponectin relationships and a decrease in the content of protective factors: adiponectin and anti-inflammatory cytokine IL-10. While the SAT adipocytes was characterized by a decrease in the concentration of soluble receptor for leptin and the more pronounced leptinresistance, and the increase in proinflammatory cytokines was offset by the increase in the concentration of IL-10. The presence associated with multi-vessel coronary bed lesion, multifocal atherosclerosis, insulin resistance, atherogenic dyslipidemia, an imbalance of adipokines and markers of inflammation. So the value of the square VAT determined higher concentrations of leptin, TNF-α in adipocytes and serum, lipid and carbohydrate metabolism and a lower content of soluble receptor for leptin. Thus, the disease on the background of the status of the adipocytes of EAT characterized as a &quot;metabolic inflammation&quot;, and may indicate the direct involvement of adipocytes in the pathogenesis of coronary artery disease, due to the formation of adipokine imbalance and the activation of proinflammatory reactions.

A drop in the circulating concentrations of soluble receptor for advanced glycation end products is associated with seroconversion to autoantibody positivity but not with subsequent progression to clinical disease in children en route to type 1 diabetes.

Advanced glycation end products (AGEs) and their interaction with the receptor for AGEs (RAGE) have been studied for their role in the pathogenesis and complications of type 1 diabetes. Decreased concentrations of soluble RAGE (sRAGE) have been reported in acute autoimmune inflammation. We set out to analyze the changes in sRAGE concentration during preclinical diabetes in children seroconverting to islet autoantibody positivity. We measured serum concentrations of sRAGE in 168 children who progressed to clinical disease and 43 children who turned positive for at least 2 diabetes-associated autoantibodies but remained nondiabetic. We analyzed the sRAGE before seroconversion in the first autoantibody-positive sample and annually thereafter until the diagnosis of type 1 diabetes or end of follow-up. Both groups had similar sRAGE before seroconversion, but subsequently, sRAGE concentrations were lower (P<.001) in the progressors. The progressors had significantly higher sRAGE concentrations before than after seroconversion (P<.001). The nonprogressors did not experience a similar decrease. The sRAGE concentrations remained stable after seroconversion in both groups. These data indicate that sRAGE may be involved in the initiation of beta-cell autoimmunity but not in the progression from beta-cell autoimmunity to clinical disease.

A study of extracellular vesicle concentration in active diabetic Charcot neuroarthropathy

It was the aim of this work to determine whether the plasma concentration of extracellular vesicles (EVs) in active diabetic Charcot neuroarthropathy (CN) is connected to the inflammatory markers, temperature elevation in the affected foot and concentration of soluble receptor for advanced glycation end products (RAGE). EVs were isolated from peripheral blood of 35 patients with active CN. EVs were counted after repetitive centrifugation and washing of samples, by flow cytometry. Foot temperature was measured by infrared thermometer. Concentration of soluble receptor for advanced glycation end products (RAGE) was determined by enzyme-linked immunosorbent assay (ELISA). We found statistically significant correlations of EV concentration (but not soluble RAGE concentration) with C-Reactive Protein (CRP) and with temperature difference between the affected and the contralateral foot (r=0.40, p=0.032; r=0.89, p<10−8, respectively). We provide evidence that the concentration of EVs is related to elevation of markers of inflammation (CRP and foot temperature difference) in acute Diabetic CN. EV-based markers could be considered as a potential aid in early diagnosis of CN.

Distinct Profiles of Soluble Cytokine Receptors Between B-Cell Vitreoretinal Lymphoma and Uveitis.

To determine the profiles of soluble cytokine receptors and cytokines, including mostly their ligands, in the vitreous humor of patients with B-cell vitreoretinal lymphoma (VRL) and uveitis. Vitreous samples were collected from immunocompetent patients with VRL (n = 21), uveitis (n = 20), and idiopathic epiretinal membrane (n = 21) as controls. Cytometric beads assay were used to determine the vitreous concentrations of soluble receptors and cytokines. Vitreous levels of soluble IL-2 receptor α (sIL-2Rα), sIL-6R, soluble tumor necrosis factor receptor (TNFR) 1, sTNFR2, soluble vascular endothelial growth factor receptor (sVEGFR) 1, sVEGFR2, and IL-10 were higher in patients with VRL than in those with uveitis and controls, whereas those of sIL-1R1, sIL-1R2, and sIL-4R were higher in patients with uveitis than those with VRL and controls. In analyses in patients with VRL, elevation of sVEGFR1 and sVEGFR2 levels was more prominent in patients with systemic metastatic retinal lymphoma (SMRL) than in those with primary VRL/primary central nervous system lymphoma (PVRL/PCNSL). Furthermore, sIL-2Rα levels were increased in patients with VRL who developed subretinal lesions compared with in those who mainly had vitreous cavity opacity, positively correlated with the density of CD3+ cells in the vitrectomy cell blocks. The profiles of soluble cytokine receptors and cytokines in patients with VRL were different from those with uveitis. In addition, sVEGFR1 and sVEGFR2 levels may be differential diagnostic markers between PVRL/PCNSL and SMRL, and sIL-2Rα levels can anticipate infiltration of VRL cells into the subretina and/or retina.

Decrease in circulating concentrations of soluble receptors for advanced glycation end products at the time of seroconversion to autoantibody positivity in children with prediabetes.

Dietary advanced glycation end products (AGEs) and their interactions with the receptor for AGEs (RAGE) may play a role in the pathogenesis of type 1 diabetes. This study set out to assess whether there is any association of circulating concentrations of soluble RAGE (sRAGE), AGEs, and their ratio with the appearance of diabetes-associated autoantibodies in children progressing to clinical diabetes. Serum concentrations of sRAGE, N-ε(carboxymethyl)lysine (CML) adducts, and the sRAGE/CML ratio were analyzed in children who progressed to type 1 diabetes. The samples were taken at four time points: before seroconversion, at the time of the first autoantibody-positive sample, at the time of the first sample positive for multiple (>2) autoantibodies, and close to the disease diagnosis. Samples of autoantibody-negative controls matched for age, sex, and HLA-conferred diabetes risk were analyzed at corresponding time points. The prediabetic children had higher sRAGE concentrations before seroconversion (Pc = 0.03), at the appearance of multiple autoantibodies (Pc = 0.008), and close to diagnosis (Pc = 0.04). Close to diagnosis, the cases had lower CML concentrations than the controls (Pc = 0.004). Prediabetic children had a higher sRAGE/CML ratio than the controls before seroconversion (Pc = 0.008) and at diagnosis (Pc < 0.001). Prediabetic children have higher concentrations of sRAGE and a higher sRAGE/CML ratio than healthy controls. Circulating sRAGE concentrations seem to decline with the appearance of diabetes-predictive autoantibodies in children progressing to type 1 diabetes. The higher sRAGE/CML ratio in prediabetic children may reflect a higher AGE scavenger capacity.

Circulating concentrations of soluble receptor for AGE are associated with age and AGER gene polymorphisms in children with newly diagnosed type 1 diabetes.

We analyzed the relationship among soluble receptor for advanced glycation end products (sRAGEs), the clinical phenotype, HLA genotype, and risk-associated single nucleotide polymorphisms (SNPs) in the AGER gene in a large population of Finnish children with newly diagnosed type 1 diabetes. Samples from 2,115 clinically phenotyped children <15 years of age in whom type 1 diabetes was diagnosed and 316 control subjects were analyzed for sRAGEs. Three SNPs of AGER, previously associated with HLA-DR/DQ haplotype independent diabetes risk (rs2070600, rs9469089, and rs17493811), were analyzed in 1,390 affected subjects. Children with type 1 diabetes and control subjects had similar sRAGE concentrations (1,171 vs. 1,153 pg/mL, P = 0.48). There was a correlation between age at diagnosis and serum sRAGE concentrations (r = 0.10, P < 0.001) among the patients but not among the control subjects. Children <2 years of age had the lowest concentrations in the diabetic population (1,027 vs. 1,181 pg/mL, P < 0.001) and the highest among the control subjects (1,329 vs. 1,140 pg/mL, P = 0.04). Ketoacidosis at diagnosis was associated with reduced concentrations (1,086 vs. 1,190 pg/mL, P < 0.001). HLA DR3/DR4 heterozygosity and the DR3 allele were associated with reduced sRAGE concentrations. The predisposing AA genotype of rs2070600 was associated with decreased sRAGE concentrations, while the protective CC genotype of rs9469089 was linked to increased concentrations. Age and AGER polymorphisms are associated with the circulating sRAGE concentration among children with type 1 diabetes. The observations of reduced sRAGE concentrations in young children, in those with ketoacidosis, and in carriers of the high-risk HLA DR3/DR4 genotype suggest that decreased sRAGE concentration reflects a more aggressive disease phenotype.

Plasma cytokine profiles in HIV-1 infected patients developing neuropathic symptoms shortly after commencing antiretroviral therapy: a case-control study

BackgroundIn patients infected with human immunodeficiency virus 1 (HIV-1) neuropathic symptoms may develop within weeks of starting combination antiretroviral therapy (cART). This timing coincides with the occurrence of immune reconstitution inflammatory syndrome. Our objective was to investigate the longitudinal association of plasma cytokine and soluble receptor concentrations with incident neuropathic symptoms within 12 weeks of starting programme-based cART in a nested case-control study.MethodsOne hundred and twenty adults without neuropathic symptoms and about to initiate cART were followed longitudinally for 24 weeks after cART initiation. Subjects were examined for peripheral neuropathy at baseline (pre-cART) and 2-, 4-, 12- and 24 weeks thereafter. Individuals developing neuropathic symptoms within 12 weeks of starting cART were matched in a nested case-control design with those remaining symptom-free for at least 24 weeks. Plasma was collected at each visit. Cytokines and soluble receptors were quantified using multiplex immunometric assays.ResultsIncident neuropathic symptoms occurred in 32 (27%) individuals within 12 weeks of starting cART for the first time. Cytokine concentrations increased at 2 weeks, irrespective of symptom-status, returning to baseline concentrations at 12 weeks. Compared to the control group, the symptomatic group had higher baseline levels of interleukin-1 receptor (IL-1R)-antagonist. The symptomatic group also showed greater increases in soluble interleukin-2 receptor-alpha and tumour necrosis factor (TNF) receptor-II levels at week 2 and soluble interleukin-6 receptor levels at week 12. Ratios of pro-inflammatory- vs anti-inflammatory cytokines were higher for TNF-alpha/IL-4 (p = 0.022) and interferon-gamma/IL-10 (p = 0.044) in those developing symptoms. After 24 weeks of cART, the symptomatic group showed higher CD4+ counts (p = 0.002).ConclusionsThe initiation of cART in previously treatment naïve individuals was associated with a cytokine 'burst’ between 2- and 4 weeks compared with pre-cART levels. Individuals developing neuropathic symptoms within 12 weeks of starting cART showed evidence of altered cytokine concentrations even prior to initiating cART, most notably higher circulating IL-1R-antagonist levels, and altered ratios of “pain-associated” cytokine and soluble receptors shortly after cART initiation.

Hemophagocytic syndrome in children and adults.

Hemophagocytic syndrome, also known as hemophagocytic lymphohistiocytosis (HLH), is a heterogenic syndrome, which leads to an acute, life-threatening inflammatory reaction. HLH occurs both in children and adults, and can be triggered by various inherited as well as acquired factors. Depending on the etiology, HLH can be divided into genetic (i.e., primary) and acquired (i.e., secondary) forms. Among genetic HLH forms, one can distinguish between familial HLH and other genetically conditioned forms of HLH. Acquired HLH can be typically triggered by infections, autoimmune diseases, and malignancies. The most common symptoms of HLH are unremitting fever, splenomegaly, and peripheral blood cytopenia. Some severely ill patients present with central nervous system involvement. Laboratory tests reveal hyperferritinemia (often >10,000 μg/L), increased serum concentration of soluble receptor α for interleukin-2 (>2,400 U/L), hypertriglyceridemia, hypofibrinogenemia, coagulopathy, hyponatremia, hypoproteinemia, and elevated liver transaminases and bilirubin. Prognosis in HLH is very serious. Genetic HLH is always lethal if adequate therapy is not administered. Similarly, severe acquired cases often lead to death without appropriate treatment. Since HLH can be encountered by various specialists in the medical field, basic knowledge of this entity such as diagnostic criteria and treatment should be familiar to all physicians.

Inflammatory Status in Patients with Metabolic Syndrome

We read the article ‘The influence of chosen adipocytokines on blood pressure values in patients with metabolic syndrome’ written by Musialik et al. with interest [1]. The authors aimed to investigate the impact of chosen adipocytokines, such as adiponectin, tumour necrosis factor alpha (TNF-α) receptors (sTNFR1, sTNFR2), and resistin, on the development of high blood pressure (BP), which is a significant risk factor for cardiovascular events. They concluded that the concentration of adiponectin was markedly lower in patients with metabolic syndrome (MetS) compared to the control group. In patients with MetS, sTNFR1 and sTNFR2 concentrations were significantly elevated and resistin level was significantly higher compared to control subjects. Negative correlations between adiponectin and the values of systolic (SBP) and diastolic (DBP) blood pressure were observed. Positive correlations between sTNFR2 and SBP and DBP values were found. Resistin levels correlated positively with SBP and DBP values. In a multiple regression model, the association of SBP with resistin level was observed in 32% of studied patients. They suggested that patients with MetS are diagnosed by the following disturbances: hypo- -adiponectinaemia, elevated concentrations of soluble receptors for TNF-α, and hyperresistinaemia. Increased concentration of resistin may play a role in the development of high blood pressure.Metabolic syndrome is a clinical entity comprising risk factors such as hypertension, glucose intolerance, atherogenic lipid profile, abdominal obesity, lack of physical activity, and increased inflammatory state. According to data from a previous study, MetS is described in more than 20% of men and 17% of women [2]. Most recent studies have demonstrated a correla-tion between inflammatory mediators and components of MetS. Particularly, interleukin 6 (IL-6), TNF-α, and C-reactive protein (CRP) levels have been observed to increase in MetS [3]. Another study has reported the association between the inflammatory markers and the severity of MetS [4]. These parameters indicat-ing inflammation in MetS may be early markers of developing cardiovascular events. Although the authors have shown that patients with MetS had significantly higher inflammatory mediators compared to those without MetS, they did not mention inflammatory mediators’ status according to severity of MetS in the present study. Elevated inflammatory mediators is a common indicator of atherosclerotic involvement of the vascular structure indicat-ing coronary artery disease, cerebrovascular disease, peripheral arterial disease and chronic inflammatory disease [5]. It can also be affected by the atherosclerotic risk factors such as smoking, alcohol consumption, hypercholesterolaemia, and hypothyroi-dism. The authors did not discuss in this study some of the factors affecting these markers, including smoking, alcohol consumption, insulin resistance, hypercholesterolaemia, hypothyroidism, heart failure, cerebrovascular disease, peripheral arterial disease and chronic inflammatory disease. It would be better if the authors had given information about these factors. In addition, the au-thors did not define clearly that MetS is independently associated with inflammatory parameters. It would be better if the authors had made a multivariate regression analysis, and adjusted for other related factors (e.g. smoking, hypercholesterolaemia, medications, and chronic inflammatory disease).Secondly, some medications such as antihypertensive treatment (including angiotensin-converting enzyme inhibitors, angiotensin receptor blocker, b-blocker), statins, medications for weight loss, and a medical history of drug addiction may influ-ence inflammatory mediators. It would be useful, and results might be different, if the authors had described these factors. Furthermore, the presence of MetS may be associated with many factors, including socioeconomic and lifestyle factors. Indi-viduals with a low level of education and of low socioeconomic status have been shown to be at a higher risk of MetS. They are usually characterised by incorrect dietary habits, low levels of physical activity and high levels of harmful habits, all of which increase the risk of metabolic abnormalities [6]. If these factors had been mentioned in the present study, its results would have been more robust.

Effect of psoriasis activity on VEGF and its soluble receptors concentrations in serum and plaque scales

Vascular endothelial growth factor (VEGF) demonstrating pro-angiogenic activity promote new blood vessel formation in psoriatic lesions. The aim of this study was to evaluate the serum concentrations of VEGF, its soluble receptors (sVEGF R1 and R2) and VEGF content in scales of patients with psoriasis. To analyze possible association with activity of the disease, serum and scales from plaques were collected from 59 patients with exacerbated chronic plaque-type psoriasis. Mean concentrations of VEGF and sVEGF R1 in sera of patients were respectively two and four times higher than in healthy controls. Serum VEGF and sVEGF R1, but not sVEGF R2 demonstrated significant correlation with psoriasis area and severity index (PASI). There was also significant correlation between VEGF levels in serum and scales. Serum sVEGF R1 concentration was significantly elevated even in patients with low psoriasis activity (PASI < 10), whereas increase of serum VEGF became significant in patients with medium activity (PASI: 10–20). Levels of serum VEGF and sVEGF R1 were the highest in patients with PASI > 20. We confirmed association of both serum and scales VEGF concentrations with degree of psoriasis activity and demonstrated predominant increase of sVEGF R1 vs. VEGF in serum of patients with low psoriasis activity.

Serum Concentrations of TNF α and Its Soluble Receptors in Patients with Adrenal Tumors Treated by Surgery

The peripheral blood levels of TNF α and its soluble receptors were studied in 39 patients with malignant and benign adrenal tumors treated by adrenalectomy. The concentrations of TNF α were significantly elevated in patients with malignant tumors of the adrenal cortex and in patients with Conn’s syndrome compared to control. In patients with non-functioning adenomas and pheochromocytomas, TNF α levels were similar to those detected in the control. In subjects with myelolipomas, the serum concentration of TNF α was lower compared to the control. After adrenalectomy, the levels of TNF α were decreased in patients with malignant tumors and in patients with Conn’s syndrome, nonfunctioniong adenomas and pheochromocytomas compared to the concentration before surgery. The serum concentrations of soluble receptors of TNF α did not differ among different patient groups and compared to the control. After adrenalectomy, the blood concentrations of TNF α R1 and TNF α R2 were decreased in patients with Conn’s syndrome. However, to confirm practicality of the evaluation of TNF α and its soluble receptors in differential diagnosis in patients with adrenal tumors, a larger study group is needed.

Follicle‐stimulating hormone (FSH), interleukin‐1 (IL‐1) and bone density in adult women

This study tested the hypothesis that FSH promotes bone loss by inducing secretion of bone‐resorbing cytokines or by altering their receptor expression. Thirty six women (20–50 years old) were assessed for bone mineral density (BMD), circulating FSH, cytokine and soluble receptor concentrations, and expression of cytokine receptors on monocytes. Isolated mononuclear cells were also incubated in vitro with FSH. The results indicated that BMD was inversely related to serum FSH (R: −0.36 to −0.52, P: 0.03 to 0.001, depending upon skeletal site), and also related to physical activity and body composition. FSH induced mononuclear cells to secrete IL‐1β in proportion to the expression of FSH receptors on the monocytes, and serum FSH correlated with plasma IL‐1β. The ratio of plasma IL‐1β to IL‐1 receptor antagonist (IL‐1Ra) was inversely related to BMD (R = −0.53, P = 0.002) in all but the most physically‐active women, who had lower IL‐1 type I receptor expression relative to type II (decoy receptors, P = 0.01). Physical activity correlated with soluble IL‐1 receptor secretion (R = 0.53, P = 0.003) and IL‐1Ra correlated with % body fat (R = 0.66, P &lt; 0.0001). In conclusion, BMD is related to serum FSH, physical activity and body composition. Although these factors have direct effects on BMD, the present study suggests that each may also influence BMD by modulating the activity of IL‐1β. Supported by NIH grant AG027714.