Alterations in serum levels of IL-17 in contrast to TNF-alpha correspond to disease-modifying treatment in relapsing-remitting multiple sclerosis

Cytokines of different types play an important role in multiple sclerosis (MS) pathogenesis as mediators and regulators of the immune processes in the central nervous system. The aim of the study was to determine the effect of interferon-beta and glatiramer acetate on serum concentrations of TNF-alpha and IL-17?A and their correlation with the degree of disability in clinically stable patients with relapsing-remitting MS. A cross-sectional, case-control study of 220 patients (68 treatment naïve; 152 treated with interferon-beta or glatiramer acetate) and 99 clinically healthy age-gender-body mass index-matched subjects were performed. Serum cytokine concentrations were measured during remission of the disease by means of ELISA. Treatment naïve patients showed significantly higher levels of IL-17?A than the treated individuals (p?=?.000109) and controls (p?=?.000044). Within the treated group, only patients with interferon-beta had significantly higher serum IL-17 than the controls (p?=?.023). TNF-alpha concentrations were significantly higher in the treated patients compared to the healthy controls (p?=?.000013), regardless of the type of the therapy. Treatment naïve individuals did not differ from the controls according to their serum TNF-alpha (p?=?.922). No correlation was found between the serum cytokine concentrations and Expanded Disability Status Scale (EDSS) score (p?>?.05). Serum concentrations of these cytokines could not be regarded as reliable predictors for the severity of the residual neurological deficit during disease-modifying treatment. Our data suggest that suppression of IL-17?A production as one of the mechanisms underlying the beneficial effect of first-line disease-modifying treatments is stronger in glatiramer acetate than in interferon-beta.     

The relationship between inflammation,endothelial dysfunction and proteinuria in patients with diabetic nephropathy

Abstract

Objectives. Diabetic nephropathy (DN) is a major manifestation of microangiopathy in patients with Diabetes Mellitus (DM). Inflammation is one of the major factors in the formation of endothelial dysfunction. Endothelial dysfunction is a major contributor to the complications of DM. The aim of the present study was to investigate the possible relationship between inflammation, endothelial dysfunction and proteinuria in patients with diabetic nephropathy. Materials and methods. Plasma TNF-α and IL-6, pro-inflammatory cytokines, concentrations were measured in 25 patients with DN and in 30 diabetic control subjects. Also, we evaluated the markers of endothelial dysfunction such as flow mediated dilatation (FMD), nitrate-mediated dilatation (NMD) and carotid intima-media thickness (CIMT). Results. TNF-α, IL-6 and high-sensitivity C-reactive protein concentrations were significantly higher (p = 0.012, p = 0.006 and p < 0.001, respectively) in the patients with DN than the controls. And, urinary protein concentrations were significantly higher (p < 0.001) but eGFR levels were significantly lower (p < 0.001) in the patients with DN. FMD was significantly lower in DN patients (p < 0.001). We have observed that FMD correlated negatively with body mass index (r = ?0.424, p < 0.05). And there was also a positive correlation between TNF-α and urinary protein concentrations in the patients with DN (p < 0.05). Conclusion. TNF-α, IL-6, hsCRP and urinary protein concentrations are higher in the DN patients. There were no correlations among pro-inflammatory cytokines concentrations and markers of vascular endotelial disfunction. These findings did not show vascular endothelial dysfunction, but may indicate glomerular endothelial dysfunction.     

A Comparison of Three Methods,Utilizing Different Principles,for the Determination of Uric Acid in Biological Fluids

Abstract

Objective: The aim of the study was to compare endocrine parameters such as leptin, visfatin, insulin resistance, exercise capacity and body composition change, the pulmonary functions test (PFT) and arterial blood gases (ABG) parameters of chronic obstructive pulmonary disease (COPD) patients and in healthy controls. Materials and method: Fifty-five patients with COPD and without malnutrition and 25 healthy controls were included in our study. The serum leptin, visfatin, tumor necrosis factor alpha (TNF-α) and insulin resistance, body fat-free mass (FFM) and fat mass (FM) were measured in the groups. Additionally, body mass index (BMI) was calculated and the 6-minute walk test (6MWT), PFT and ABG analyses were performed in all of the cases. Results: No difference in BMI between the COPD group and controls was determined. Serum leptin and visfatin levels, FFM and 6MWT distance were significantly lower in the patients with COPD (p < 0.001, p = 0.001, p = 0.032, p < 0.001, respectively). A correlation was found between serum leptin levels and BMI (r = 0.333, p = 0.027), and with FM (r = 0.365, p = 0.029). Serum visfatin level was correlated with the percentage of forced expiratory volume in the first second in the patients with COPD (r = 0.371, p = 0.013). HOMA-IR (Homeostasis model assessment of insulin resistance) and serum TNF-α levels in the patients with COPD were found to be significantly higher than controls (p = 0.001, p < 0.001). Conclusion: These results may be earlier signs for further diseases that can emerge in the advanced stages in patients with COPD. Evaluating the patients not only with the pulmonary function and also systemically, contributes to minimizing the mortality and morbidity.     

Heparin and EDTA anticoagulants differentially affect the plasma cytokine levels in humans

Abstract

Cytokines and chemokines are the cell signaling proteins which are considered as important biomarkers of inflammation and immunity. However the fragile nature of these markers results in the concentration variation due to various external factors. We assessed the influence of commonly used anticoagulants (EDTA and heparin) on various cytokine levels from 32 paired plasma samples using highly sensitive multiple cytokine estimation assay. Out of 17 cytokines estimated, 15 were detectable in more than 80% of the samples from both the groups. TNF-α, IFN-γ, IL-4, IL-5, and G-CSF levels were significantly higher (p values < 0.05 for all) in plasma with EDTA, whereas the levels of IL-6, IL-8, IL-10, IL-17, MIP-1β, GM-CSF and MCP-1 were found to be significantly higher (p values < 0.05 for all) in plasma with heparin. There was no significant difference in the levels of IL-7, IL-12 (P70) and IL-13 in both the groups. The study showed that the anticoagulants significantly affect the measurement of certain cytokines. Hence, it is important to choose an appropriate anticoagulant before the estimation of cytokines for reliable use of plasma cytokines as biomarkers in patient management.     

Aberrant cytokines/chemokines production correlate with proteinuria in patients with overt diabetic nephropathy

BackgroundDiabetic nephropathy (DN) occurs in 20% to 30% of all patients with type 2 diabetes mellitus (DM) and is the most common cause of end-stage renal disease. However, the definite pathogenesis, especially the role of immune response, is still unclear.MethodsWe studied the production and expression of Th1 (IFN-γ, IL-2R), Th2 (IL-4, IL-10), proinflammatory cytokines (IL-1β, and TNF-α), and chemokines (MCP-1, and RANTES) in patients with DN. The correlation among cytokines, chemokines, and clinical parameters were examined.ResultsA patient with DN presented with longer disease duration, heavy proteinuria, and impaired renal function. Our results demonstrated increased proinflammatory cytokines, Th1 cytokines and chemokines, but not Th2 cytokines, in the plasma and urine of patients with DN as compared to patients with DM without overt nephropathy. Enhanced cytokine/chemokine activation in DN was also demonstrated by positive immunohistochemical staining of kidney tissue. We found a positive correlation between daily protein loss and plasma IFN-γ and IL-2R, and urinary MCP-1, as well as a negative correlation between creatinine clearance and plasma TNF-α and urinary MCP-1.ConclusionsThere were aberrant cytokines/chemokines production correlated with the degree of proteinuria in patient with overt DN and gross proteinuria. Inflammation may be important in the pathogenesis of DN.     

T helper cell subset ratios in patients with severe sepsis

Background: T helper 1 (Th1) lymphocytes produce interferon γ (IFNγ), favouring cell mediated immunity; Th2 cells secrete interleukin-4 (IL-4), favouring humoral immunity. Cytokines produced in sepsis may effect Th subset predominance and subsequent immune responses. Methods: We measured Th subsets in ten patients with severe sepsis, seven APACHE II score-matched non-septic critically ill control patients, and ten healthy subjects. Mononuclear leukocytes were isolated and Th subsets identified by flow cytometry. Results: The median (range) Th1/Th2 ratio was 0.46 (0.2–2.5) in patients with sepsis, which was significantly lower than both non-septic controls (median 2.5 (0.2–5.9), p = 0.050) and healthy subjects (median 3.9 (1.2–10.8), p = 0.01). Conclusions: In patients with sepsis, Th2 antibody mediated (humoral) immune responses predominate. This type of response may lead to fibroblast activation and ultimately immunosuppression. Modulation of Th cell subset predominance may present a novel therapeutic option in the treatment of severe sepsis. Received: 26 May 1998 Final revision received: 9 October 1998 Accepted: 16 October 1998     

Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post-hoc analysis of a randomized controlled trial

BackgroundCytokines are involved in the development of metabolic abnormalities that may result in metabolic syndrome (MetS). Since curcumin has shown anti-inflammatory properties, the aim of this study was to evaluate the effect of curcumin supplementation on serum cytokines concentrations in subjects with MetS.MethodsThis study was a post-hoc analysis of a randomized controlled trial in which males and females with diagnosis of MetS, according to the criteria defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines, were studied. Subjects who met the inclusion criteria were randomly assigned to either curcumin (daily dose of 1 g/day) or a matched placebo for a period of 8 weeks.ResultsOne hundred and seventeen subjects were assigned to either curcumin (n = 59) or placebo (n = 58) groups. Within-group analysis revealed significant reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 following curcumin supplementation (p < 0.001). In the placebo group, serum levels of TGF-β were decreased (p = 0.003) but those of IL-6 (p = 0.735), TNF-α (p = 0.138) and MCP-1 (p = 0.832) remained unaltered by the end of study. Between-group comparison suggested significantly greater reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 in the curcumin versus placebo group (p < 0.001). Apart from IL-6, changes in other parameters remained statistically significant after adjustment for potential confounders including changes in serum lipids and glucose levels, and baseline serum concentration of the cytokines.ConclusionResults of the present study suggest that curcumin supplementation significantly decreases serum concentrations of pro-inflammatory cytokines in subjects with MetS.     

Cytokines and Cardiomyocyte Death

Cytokines have been associated with the pathogenesis of acute coronary syndromes and chronic heart failure (CHF), which are both associated with cardiomyocyte loss. In CHF, increased serum concentrations of proinflammatory cytokines, including tumour necrosis factor α (TNF-α) and also soluble TNF receptor have been found. Both TNF and Fas-ligand have been able to induce programmed cell death (apoptosis) of cardio-myocytes in various experimental studies. In ischaemic conditions of the heart, increased serum levels of soluble Fas receptor have been found. The proinflammatory cytokines interleukin 1 (IL-1), IL-2 and interferon-γ can induce TNF production from target cells, including myocytes. TNF and some other cytokines are able to induce nitric oxide production, which depresses cardiac function and can induce apoptosis. However, anti-inflammatory cytokines such as IL-10, IL-4 and IL-13, secreted by T-helper type 2 lymphocytes and other cells, inhibit the production of proinflammatory cytokines. Preliminary studies suggest that cardiotrophin-1, produced by cardiomyocytes, is able to inhibit cytokine-induced cardiomyocyte apoptosis in vitro. As growth hormone is able to inhibit the production of proinflammatory cytokines in many cell types, it may also play an important role in the regulation of apoptosis induced by these cytokines. When the cytokine-induced pathways leading to altered gene expression of cardiomyocytes are understood, this knowledge may aid in the development of drugs that prevent progressive cardiomyocyte loss, in particular by inhibiting cytokine-induced apoptosis.     

Granulocyte colony‐stimulating factor produces a decrease in IFNγ and increase in IL‐4 when administrated to healthy donors

Hematopoietic stem cells transplantation (HSCT) is the leading curative therapy for a variety of hematological and hereditary diseases; however, graft versus host disease (GVHD), an immunologic phenomenon that is favored by Th1 cytokines and cytotoxic cells from donors, is present frequently and is one of the most important causes of transplant related mortality. Peripheral blood HSCT is the preferred source of stem cells in almost 100% of the cases of autologous HSCT and in 70% of allogeneic transplants. The best mobilizing agent to get the stem cells out from the bone marrow is the Granulocyte‐Colony Stimulating Factor (G‐CSF). In this work, our main objective was to study a possible correlation between the graft cell dose and the patient's clinical outcome. We evaluated the immunologic changes produced by G‐CSF in the lymphocyte and cytokine profiles in allogeneic HSC donors. HSC from twelve donors were mobilized with G‐CSF at 16 μg/kg/day, for 5 days. Basal Peripheral Blood (BPB), Mobilized Peripheral Blood (MPB), and aphaeresis mononuclear cells (G‐MNC) samples were taken from all donors. Using flow cytometry, we quantified CD19⁺, CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺, NK, NKT, DC1, and DC2 cells. Cytokines were determined by ELISA in culture supernatants. CD19⁺ (p = 0.001), DC1 (p < 0.002) and DC2 (p < 0.001) cells were increased in MPB with respect to BPB. An increase in Th2 cytokines such as (IL‐4) and a decrease in Th1 cytokines (IFNγ, IL‐2) were also found in MPB samples. In conclusion, Th1 and Th2 cytokines are relevant in predicting the clinical outcome after allogeneic peripheral blood HSCT. J. Clin. Apheresis 25:181–187, 2010. © 2010 Wiley‐Liss, Inc.     

先兆流产孕妇Th1／Th2细胞因子平衡状况分析

目的探讨辅助T细胞1（Th1）、辅助T细胞2（Th2）型细胞因子平衡与正常妊娠及先兆流产之间的关系。方法采用酶联免疫吸附试验（ELISA）检测60例先兆流产妇女和42名正常妊娠妇女血清中Th1型细胞因子（IL-2、TNF-α及Th2型细胞因子（IL4、IL-10）的表达水平。结果与正常妊娠组相比,先兆流产组血清中IL-2和TNF-α的表达水平明显升高（P均〈0．05）;而2组之间IL-4和IL-10的表达水平差异无统计学意义（P〉0．05）。Th1型细胞因子与Th2型细胞因子平衡向Th1的方向移动。结论Th1／Th2型细胞因子的病理性失衡可能与先兆流产的发生有-定关系。     

Effects of Apnea,Obesity, and Statin Therapy on Proprotein Convertase Subtilisin/Kexin 9 Levels in Patients with Obstructive Sleep Apnea

ObjectivesObstructive sleep apnea (OSA) is a common condition closely related to obesity, insulin resistance, dyslipidemia, and cardiovascular disease. The aim of this study was to explore the possible relationship between OSA and proprotein convertase subtilisin/kexin type 9 (PCSK9).MethodsFull-night polysomnography was performed on 150 participants who were divided into three groups: controls, OSA patients on statin therapy, and OSA patients not on statin therapy. Biochemical markers, plasma low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses, and PCSK9 were determined.ResultsPCSK9 was highest in OSA patients on statins compared to the control group and to OSA patients not on statins (p = 0.036 and p = 0.039, respectively), after adjustment for body mass index (BMI). LDL diameter was greater in OSA patients not on statins compared to OSA patients on statins (p = 0.032). PCSK9 was highest in the group of patients with all three risk factors (diagnosed OSA, statins, BMI ≥25 kg/m²) compared to groups with no, one, and two risk factors (p = 0.031, p = 0.001, and p = 0.029, respectively). Presence of OSA, statin therapy, and BMI ≥25 kg/m² when combined were independently associated with higher levels of PCSK9 when adjusted for antihypertensive therapy, small dense LDL, and HDL 3c subclass (odds ratio = 2.849; interquartile range [1.026–7.912], p = 0.044).ConclusionStatin therapy was closely related to PCSK9. OSA along with obesity and statin use induces elevation of PCSK9.     

Postload hyperglycemia is associated with increased subclinical inflammation in patients with prediabetes

Abstract

Background/aims. In this present study, we aimed: (i) To clarify if prediabetes is associated with subclinical inflammation independent of underlying obesity, and (ii) to evaluate the effect of postload glucose concentration on subclinical inflammation markers in a group of patients with elevated fasting glucose. Material and methods. In a cohort of 165 patients with newly detected fasting hyperglycemia, according to 75 g oral glucose tolerance test (OGTT), subjects were classified either as newly diagnosed type 2 diabetes (diabetes group, n = 40), impaired fasting glucose (IFG) plus impaired glucose tolerance (IGT) (IFG/IGT group, n = 42) or IFG only (IFG group, n = 83). A control group (n = 47) consisted of age- and body mass index (BMI)-matched healthy subjects with a normal OGTT. Circulating concentrations of lipids, insulin, interleukin-6 (IL-6), interleukin-8 (IL-8) and high sensitive C-reactive protein (hsCRP) were measured. HOMA index was calculated. Results. Subclinical inflammation markers were elevated in patients with diabetes and IFG/IGT compared to healthy controls and also IFG patients (diabetes vs. control: p < 0.05 for hsCRP, IL-8, and IL-6; IFG/IGT vs. control: p < 0.05 for hsCRP, and IL-6; diabetes vs. IFG: p < 0.05 for hsCRP, and IL-6; IFG/IGT vs. IFG: p < 0.05 for hsCRP, and IL-6). In multiple regression analysis, postload glucose concentration was independently associated with circulating hsCRP and IL-6 concentrations when the data was controlled for age, gender, BMI and lipid concentrations (p < 0.05 for hsCRP, and IL-6). Conclusion. Our results suggest that patients with prediabetes, independent of underlying obesity, have increased concentrations of subclinical inflammation which is mostly driven by postload glucose concentrations.     

Transient elevation of neutrophil proteinases in induced sputum during COPD exacerbation

Objective. Patients with chronic obstructive pulmonary disease (COPD) are prone to acute exacerbations associated with increased morbidity and mortality. One potential group of enzymes causing tissue destruction in this disease includes neutrophil proteinase elastase (NE), collagenase‐2 (matrix metalloproteinase‐8 (MMP‐8)) and gelatinase B (MMP‐9). We investigated the activity of NE and the levels of MMP‐8 and MMP‐9 in a longitudinal setting at and after COPD exacerbation using a non‐invasive technique, i.e. induced sputum, to ascertain whether these proteinases play a role in COPD exacerbation. Material and methods. The study included healthy non‐smokers (n = 32), healthy smokers (n = 28), patients with stable COPD (n = 15), COPD patients with acute exacerbations (exa) (n = 10) and their recovery (n = 8) after 4 weeks. NE activity by synthetic peptide substrate and spectrophotometry, MMP‐8 levels by immunofluorometry and MMP‐9 levels by ELISA were analysed from induced sputum supernatants. Results. NE activity and the level of MMP‐8 increased highly significantly in patients with COPD exacerbation compared to stable COPD and controls (NE: p = 0.001 and p<0.0001; MMP‐8: p<0.001 and p<0.0001). Paired samples showed a decrease of these proteinases during the recovery period after exacerbation (p = 0.03, p = 0.04). The proteinase levels correlated not only with the percentage and number of neutrophils but also with the lung function parameters (FEV1/FVC and diffusion capacity). Conclusions. COPD exacerbations are associated with neutrophil recruitment into the airways but also transient activation and/or elevation of tissue destruction proteinases, such as NE and MMP‐8, which can be detected from the induced sputum supernatants of these COPD patients.     

Osteopontin as a marker of weight loss in lung cancer

Abstract

Although the role of osteopontin (OPN) in tumorigenesis and invasiveness is well-known, its role in systemic consequences of lung cancer has not been studied yet. The objective of the current study was to assess the value of osteopontin as a marker of weight loss in relation to systemic inflammation in non-small cell lung cancer (NSCLC) patients. A total of 63 male NSCLC patients (stage III and IV) and 25 age and sex-matched controls were included. The NSCLC patients were further divided into subgroups depending on whether they had > 5% weight loss in the last 6 months or not. Serum OPN and TNF-α concentrations were measured by ELISA using commercially available kits. Serum C-reactive protein (CRP) concentration was measured by the turbidimetric method. OPN (p = 0.001) and CRP (p < 0.001) concentrations were significantly higher in lung cancer patients compared to controls whereas TNF-α concentrations were similar in cancer and control groups (p = 0.063). There were 33 NSCLC patients (52.4%) with weight loss. Serum OPN concentration was found to be higher in this weight-losing group (p = 0.042). CRP concentration was also higher in the weight-losing group but the difference was not statistically significant (p = 0,246). TNF-α concentrations were similar in both subgroups (p = 0.094). In correlation tests, there was a positive correlation between OPN and CRP (r = 0.299, p = 0.044), but no correlation was detected between OPN and TNF-α (r = ? 0.009, p = 0.930). A negative correlation was detected between OPN and BMI (r = ? 0.246, p = 0.048). In addition to being an indicator of systemic inflammation in lung cancer patients, osteopontin may also be an indicator of weight loss.     

哮喘和COPD患者急性发作期痰中细胞因子IL-5、IL-13、TNF-α测定的临床意义

目的：探讨哮喘和慢性阻塞性肺疾病（COPD）患者急性发作期时痰中细胞因子白介素5（IL-5）、白介素13（IL-13）、肿瘤坏死因子α（TNF-α）的水平及其测定的临床意义。方法采用酶联免疫法和放射免疫方法对17例COPD患者、19例哮喘患者和12例健康者痰液中IL-5、IL-13和T N F-α的水平进行检测。结果哮喘急性发作期痰中IL-5、IL-13、T N F-α含量显著高于健康者（P＜0．05）。COPD患者急性发作期痰中IL-5、IL-13、TNF-α含量显著高于健康者（P＜0．05）。哮喘组痰液中IL-5、IL-13水平显著高于COPD组（P＜0．02,P＜0．05）,而TNF-α水平在两患病组中无明显差异（P＞0．05）。结论 IL-5、IL-13和 TNF-α在哮喘发病过程中起重要作用。IL-5、IL-13和TNF-α共同参与了COPD气道炎症反应。     

Effects of radiolabelled murine antibody infusion on TNF-α, IL-1β, and soluble IL-2 receptor in cancer patients

This study evaluates the plasma levels of tumor necrosis factor-α (TNF-α), interleukin- 1β (IL-1β), and soluble IL-2 receptor (sIL-2R) in cancer patients infused with radiolabelled murine monoclonal antibodies (MAbs) for the purposes of imaging and dosimetry. Blood samples were collected from 13 patients (10 with colon cancer and 3 with lung cancer) before and at 4 and 7 days after infusion of either conventional intact ¹¹¹In- MAb or a bifunctional antibody delivery system. For all subjects, except one, this was the first exposure to murine MAb. Before infusion, higher levels of TNF-α, IL-1β, and sIL-2R than the average expected in the plasma of healthy individuals were found. A significant decrease was noted in TNF-α when preinfusion concentrations were compared to 4 day (P < 0.01) or to 7 day (P < 0.05) postinfusion values. A 50% or greater decrease in IL-1β was also observed in most individuals with time after infusion. In contrast, sIL-2R concentrations remained relatively stable during the 1 week follow-up period. However, strikingly different patterns in the IL-1β and sIL-2R levels were noted in the subject who had received two previous murine antibody infusions. Our data show that the administration of radiolabelled murine antibodies, either conventional or bifunctional, can significantly alter plasma levels of TNF-α and IL-1β. These cytokines are important in immunoregulation and, perhaps also, in modulation of neoplastic growth. © 1994 Wiley-Liss, Inc.     

A new agent for tumour necrosis factor-alpha inhibition

Abstract

Background: Tumour necrosis factor-α (TNF-α) plays a central role in inflammatory cascade in Crohn's disease (CD). Our study aims to investigate the in vitro effects of dipyridamole (DP) on the TNF-α and interleukin-10 (IL-10) production in the intestinal mononuclear cells of CD patients. Material and Methods: Thirteen patients with CD and in 17 healthy individuals underwent colonoscopy and biopsy samples were taken. Cultured mononuclear cells were preincubated with DP1 (0.7 microg/ml), DP2 (1.25 microg/ml), methotrexate (MTX)1 (0.5 nmol/L) and MTX2 (1.5 nmol/L). These cells were then stimulated with lipopolysaccaride (LPS) and phytohemagglutinin (PHA). The levels of TNF-α and IL-10 in supernatants were measured with standard immunoassay monoclonal antibody method. Results: An appropriate cell culture could be obtained in 10 patients with CD and 12 healthy individuals. In LPS stimulated cells, MTX1 and MTX2 were superior to DP1 and DP2 in suppressing TNF-α in both groups. In PHA stimulated cells, while MTX1 was superior to DP1, MTX2 and DP2 had an equivalent effect in CD patients (p<0.05, p>0.05, respectively). In LPS-stimulated cells DP2 was significantly superior to MTX2 in increasing IL-10 levels in both groups (p<0.05). In PHA stimulated cells, DP1 and DP2 caused a higher increase in IL-10 levels compared with MTX1 and MTX2 in CD group (p<0.05). Conclusions: Dipyridamole suppresses TNF-α similar with MTX. It seems to be superior to MTX in increasing IL-10 levels. Addition of DP to anti-TNF medications may create a synergy in cytokine modulation.     

Effects of microwave ablation on T-cell subsets and cytokines of patients with hepatocellular carcinoma

Objectives: To investigate the effects of microwave ablation on T-lymphocyte subsets and cytokines in patients with hepatocellular carcinoma.

Material and methods: Peripheral blood was collected from 45 patients with hepatocellular carcinoma treated by microwave ablation before treatment, one week and one month after treatment. T cells (CD3+, CD4+ and CD8+?cells), CD4+?CD25+?Tregs, and CD16+?CD56+?NK cells were analyzed by flow cytometry. Levels of cytokines (IL-2, IFN-γ, TNF-α, IL-12, IL-4, IL-6, IL-8, and IL-10) were determined by a Luminex 200 analyzer.

Results: Compared with before treatment, CD3+ cells, CD4+ cells and IL-12 increased significantly at one month after the microwave ablation treatment, while IL-4, IL-10 decreased significantly.

Conclusions: Microwave ablation could relieve the suppression of immune function caused by tumors, promote the deviation of Th2/Th1, and improve immune dysfunction in patients with hepatocellular carcinoma.     

The association between serological features of chronic Chlamydia pneumoniae infection and markers of systemic inflammation and nutrition in COPD patients

Introduction: Chlamydia pneumoniae is an obligatory human pathogen involved in lower and upper airway infections, including pneumonia, bronchitis. Asymptomatic C. pneumoniae carriage is also relatively common. The association of C. pneumoniae infections with the chronic obstructive pulmonary disease (COPD) course is unclear.

Objectives: The aim of the study was to investigate the association between chronic C. pneumoniae infection and clinical features of COPD, markers of inflammation and metabolic dysfunction.

Patients and methods: The study included 59 patients with stable COPD who had no, or had?≥2 acute exacerbations during last year. The level of IgA and IgG antibody against C. pneumoniae, IL-6, IL-8, resistin, insulin, adiponectin and acyl ghrelin was measured in serum by enzyme-linked immunosorbent assay (ELISA).

Results: No differences in clinical and functional data were observed between COPD patients without serological features of C. pneumoniae infection and chronic C. pneumoniae infection. The level of anti C. pneumoniae IgA significantly correlated with IL-8, IL-6, resistin concentration in group of frequent exacerbators. IgG level correlated negatively with acetyl ghrelin and body mass index (BMI) in patients without frequent exacerbations, in contrast to frequent COPD exacerbation group where significant correlations between IgG level and BMI was demonstrated. Serum IL-6 correlated positively with resistin and insulin and negatively with adiponectin in group of patients with serological features of chronic C. pneumoniae infection only.

Conclusions: Our study showed that chronic C. pneumoniae infection does not influence the clinical course of COPD in the both study groups. Chronic C. pneumoniae infections might be associated with a distinct COPD phenotype that affects metabolic dysfunction.