Serum Concentrations Of Soluble Receptor 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.

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.

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.

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.

Inflammatory markers for ischaemic stroke

Thromb Haemost 2009; 101: 800–801 Experimental and clinical evidence accumulated since 1990 have established inflammatory processes as important contributors to atherogenesis (1). Based upon this evidence, protein markers of inflammation have been studied as non-invasive indicators of underlying atherosclerosis in apparently healthy individuals and of the risk of cardiovascular events in patients with established atherosclerotic diseases. The most extensively studied biomarker of inflammation in cardiovascular diseases is C-reactive protein (CRP), an acute phase protein that is produced predominantly by hepatocytes under the influence of cytokines such as interleukin (IL)-6 and tumour necrosis factor (TNF)-α (2). Data from more than 30 epidemiologic studies have shown a significant association between elevated serum or plasma concentrations of CRP and the prevalence of underlying atherosclerosis, the risk of recurrent cardiovascular events among patients with established disease, and the incidence of first cardiovascular events among individuals at risk for atherosclerosis (3). Although it is plausible that CRP serum levels are increased as part of the acute phase response to inflammation, experimental evidence has also raised the possibility that CRP is a direct participant in the progression of atherosclerosis and its clinical consequences (4). Indeed, CRP infusion is associated with marked elevations in markers of both inflammation, such as IL-6, IL-8, and serum amyloid A, and coagulation, such as von Willebrand factor (vWF) antigen, prothrombin F1+2, D-dimer, and plasminogen activator inhibitor type 1 (PAI-1) (5). Regarding cerebrovascular diseases, the data in the literature indicate that CRP is an independent marker for the development and progression of early carotid atherosclerotic disease (6), the risk of ischaemic stroke (7), and the prognosis after stroke (8–10). In addition to CRP, other markers of inflammation are predictors of cardiovascular disease in healthy men and women. In men, plasma IL-6 concentrations have been shown to be predictive of a future myocardial infarction (11). Among patients with unstable or stable angina or even mild angiographic coronary disease, increased serum levels of IL-18 may be an independent predictor of cardiovascular mortality (12). One analysis found that circulating serum concentrations of soluble receptors for TNF-α are correlated with coronary risk among women (13). Other studies have found an association between the serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and P-selectin and the future development or exacerbation of cardiovascular diseases (14). Elevated serum concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin also may have predictive value (14). In a study published in the current issue of Thrombosis and Haemostasis, Licata and his collaborators add to our knowledge on immuno-inflammatory markers and ischaemic stroke (15). By studying individuals with different subtypes of ischaemic stroke, classified according to the TOAST scheme, they demonstrate that plasma levels of important inflammatory molecules, such as IL-6, TNF-α, and IL-1β, are significantly higher in subjects with stroke of cardio-embolic origin than in subjects with other subtypes of stroke. In addition, they show that, in subjects with stroke, neurological deficit at admission, as measured by the Scandinavian Stroke Scale (SSS), is significantly and independently correlated to IL-6 and TNF-α plasma levels. Licata’s findings are important for several reasons. First of all, they demonstrate that different subtypes of ischaemic stroke are associated with different levels of activation of inflammatory markers. Second, the demonstration that increased plasma levels of inflammatory cytokines are particularly evident in cardio-embolic strokes provides support to the hypothesis that inflammation may be associated with atrial fibrillation and contributes to the pathogenesis of arrhythmic disorders (16). Finally, the fact that IL-6 and TNF-α plasma levels correlate with stroke subtype and SSS score suggests that the evaluation of these inflammatory markers might be useful for a better characterisation of subjects suffering from acute ischaemic cerebrovascular diseases. These findings might have important implications for the clinical management of subjects affected by ischaemic cardiovascular diseases. © 2009 Schattauer GmbH, Stuttgart

Structured Intermittent Interruption of Chronic HIV Infection Treatment with Highly Active Antiretroviral Therapy: Effects on Leptin and TNF-α

The changes in nutritional parameters and adipocytokines after structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection are analyzed. Twenty-seven patients with chronic HIV infection (median CD4+ T cell count/microl: nadir, 394; at the beginning of structured interruptions, 1041; HIV viral load: nadir, 41,521 copies/ml; at the beginning of structured interruptions <50 copies/ml; median time of previous treatment: 60 months) were evaluated during three cycles of intermittent interruptions of therapy (8 weeks on/4 weeks off). CD4+ T cell count, HIV viral load, anthropometric measures, and serum concentrations of triglycerides, cholesterol, leptin, and tumor necrosis factor and its soluble receptors I and II were determined. After the three cycles of intermittent interruptions of therapy, no significant differences in CD4+ T cell count/microl, viral load, or serum concentrations of cholesterol or triglycerides with reference to baseline values were found. A near-significant higher fatty mass (skinfold thicknesses, at the end, 121 mm, at the beginning, 100 mm, p = 0.100), combined with a significant increase of concentration of leptin (1.5 vs. 4.7 ng/ml, p = 0,044), as well as a decrease in serum concentrations of soluble receptors of tumor necrosis factor (TNFRI, 104 vs. 73 pg/ml, p = 0.022; TNFRII 253 vs. 195 pg/ml, p = 0.098) were detected. Structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection induces a valuable positive modification in markers of lipid turnover and adipose tissue mass.

Increased Serum Concentrations of Soluble Receptor for Advanced Glycation Endproducts in Patients with Type 1 Diabetes

To the Editor: The hyperglycemic state occurring in diabetes mellitus is responsible for formation and accumulation of advanced glycation endproducts (AGEs) that participate in the pathogenesis of vascular complications of diabetes mellitus (1). There is considerable interest in the receptors for AGEs (RAGE) found in many cell types, particularly those affected in diabetes. RAGE are members of the immunoglobulin family of cell surface molecules with a diverse repertoire of ligands. Interaction of AGEs with RAGE alters several cell functions through modulation of intracellular signaling, gene expression, and release of proinflammatory molecules and free radicals that contribute to the pathology of diabetic complications (2)(3). A soluble form of RAGE (sRAGE) can be measured in peripheral blood, which could result from the expression of a RAGE splice gene variant that encodes an amino-terminally truncated form of the receptor and/or from the cleavage of the native membranous receptor (4). This form may be released by several cell types, such as endothelial cells and circulating leukocytes. Because sRAGE is presumed to be a decoy for RAGE ligands …

Receptores solubles de la interleucina 2 y del factor de necrosis tumoral en la cirrosis hepática de diversas etiologías. Relación con el pronóstico y la gravedad clínica

The mechanism responsible for the beginning and progression of hepatic injury in liver cirrhosis of viral and alcoholic etiology are unknown currently. However, there are abnormalities in the immune system which may be implied in the pathogenesis. The concentrations of the soluble receptor of tumor necrosis factor (sTNF-R55) and the soluble receptor of interleukin-2 (sIL-2R) in 49 cirrhotic patients were determined by enzyme-linked inmunoassay. Patients were grouped according to the etiology (33 alcoholic and 16 viral) and prognosis (Child-Pugh classification) and they were compared with the values obtained in 26 healthy non-drinkers who made up the control group. The concentrations of sTNF-R55 and sIL-2R were significantly higher in both groups of patients when compared with controls. We found significant differences in sTNF-R55 concentrations in viral and alcoholic but not in sIL-2R concentrations. There was a positive correlation between the concentrations of both receptors and the degrees of Child-Pugh classification, as well as with albumin, total bilirubin and alkaline phosphatase (all of them parameters related to the severity and prognosis of liver cirrhosis). The serum concentrations of soluble receptors of tumor necrosis factor and interleukin-2 correlate with the prognosis of liver cirrhosis independently of its etiology. This fact may reflect the stimulation of T lymphocytes, monocytes and macrophages, in liver cirrhosis.

Neopterin, soluble receptors for interleukin-2 and tumor necrosis factor in viral cirrhosis and alcoholic cirrhosis

Abstract Alcoholic cirrhosis and viral cirrhosis are associated with alterations of immune system function and cytokine production. Our aim was to investigate whether serum concentrations of soluble receptors for interleukin-2 (sIL- 2 R) and tumor necrosis factor (55kD-type, sTNFR-55), and serum neopterin can be used as markers to establish differences in etiology and severity in liver cirrhosis and to determine whether they correlate with laboratory and clinical parameters. Thirty three patients with alcoholic and 15 with viral cirrhosis (classified according to the Child-Pugh score of severity of liver disease) and 43 healthy controls were studied. Serum concentrations of sIL2-R, sTNFR-55 and neopterin were significantly raised in patients. No significant differences between alcoholic and viral cirrhosis were found. The concentrations of sIL-2 Rand sTNFR-55 were significantly higher in patients with more severe disease. There existed correlations b&lt;!tween sIL-2R and sTNFR-55 (rs = 0.50, P &lt; 0.001) and between both soluble receptors and the Child-Pugh score (sTNF-R55: rs = 0.70, p &lt; 0.001; sIL-2R: rs = 0.33, p &lt; 0.05) and serum albumin. The results are likely to reflect that the monocyte-macrophage and T-cell functions are stimulated in patients with liver cirrhosis independently of the etiology of the disease, and the persistent activation of the immune system occurs in cirrhosis even at the end stage of the disease. Chronic immune activation might have deletereous consequences on the evolution of cirrhosis.

Microheterogeneity of acute-phase glycoproteins in patients with pulmonary sarcoidosis.

This study was designed to investigate qualitative changes in the carbohydrate side-chains of two acute-phase glycoproteins, alpha 1-acid glycoprotein (AGP) and alpha 1-antichymotrypsin (ACT), in 37 patients with pulmonary sarcoidosis. The glycosylation profile of AGP and ACT was studied using affinity immunoelectrophoresis with the lectin concanavalin A (conA). Serum concentration of soluble receptor for interleukin-2 (sIL-2R) and activity of serum angiotensin converting enzyme (ACE) were measured by specific enzyme-linked immunosorbent assay (ELISA) and enzyme kinetic assay, respectively. Rocket immunoelectrophoresis and nephelometric assay were used to determine serum concentration of AGP, ACT and C-reactive protein (CRP). In 11 patients with active disease, a decreased reactivity of AGP with conA was found as compared with controls (n = 44) and patients with nonactive sarcoidosis (n = 26). A similar tendency was seen with ACT. In the same group, increased concentrations of serum AGP and higher levels of sIL-2R were detected compared with patients with nonactive sarcoidosis. In the entire sarcoidosis group, there was a negative correlation between ACE activity and AGP and ACT affinity for conA (r = -0.6358, and r = -0.5019, respectively) and a positive correlation with sIL-2R level (r = 0.8241). In nine patients with elevated concentrations of serum CRP, no differences were found in disease activity and glycosylation profile of AGP and ACT when compared to patients with normal serum CRP. The results suggest that in active pulmonary sarcoidosis changes in the glycosylation pattern of acute-phase glycoproteins exist, which are similar in trend and magnitude to those found in other chronic inflammatory diseases. The synthesis and glycosylation of acute-phase proteins in pulmonary sarcoidosis are probably regulated independently.

Soluble Tumor Necrosis Factor Receptors as Surrogate Markers for the Assessment of Zidovudine Treatment in Asymptomatic HIV-1 Infection

In untreated, asymptomatic human immunodeficiency virus type 1 (HIV-1) infection, elevated serum concentrations of soluble receptors for tumor necrosis factor (sTNFR) types I and II are associated with progression to AIDS. To assess the utility of sTNFRs as markers for the assessment of antiretroviral treatment, sTNFRs were sequentially determined in 47 asymptomatic HIV-1-infected men, who participated in a double-blind, randomized, placebo-controlled study. Progression to AIDS or severe AIDS-related complex occurred in six zidovudine (ZDV)- and six placebo-treated subjects. During ZDV treatment (n = 28) both types of sTNFRs declined compared with baseline and placebo, whereas they increased during placebo treatment (n = 19). A sustained decline of sTNFRs occurred only in subjects who experienced no disease progression. During the first 3 months of ZDV treatment, the hazard ratio for disease progression when sTNFR type II rose above the baseline value plus 5% was significantly increased (hazard ratio: approximately 25; 95% confidence interval: approximately 1.5-400; p < 0.03). Simultaneously determined CD4+ counts and serum neopterin levels showed a similar pattern in progressors and nonprogressors. Thus, in contrast to CD4+ counts and neopterin levels, sTNFR concentrations, especially those of the type II STNFR, appear to be valuable surrogate markers for monitoring the efficacy of ZDV treatment in asymptomatic HIV-1 infection.

Soluble Receptors for Tumor Necrosis Factor as Markers of Disease Activity in Visceral Leishmaniasis

Serum concentrations of soluble receptors for tumor necrosis factor (sTNFRs) were measured before and after antimony therapy in 25 Sudanese patients with active visceral leishmaniasis (VL). Both sTNFR types I and II were significantly elevated in patients with VL compared with healthy controls from the same region and from the Netherlands (P < .01). In all 23 patients who initially responded to therapy, both sTNFR types decreased sharply, reaching and remaining at levels similar to those found in normal controls; 2 relapsed after an initial response to therapy, and their sTNFR concentrations had increased at the time of relapse. The 2 patients who did not respond to therapy had persistently elevated sTNFR levels. Tumor necrosis factor was detectable in only 16% of patients with VL. Hence, the serum concentrations of sTNFRs may be useful for monitoring therapeutic efficacy in patients with VL.