Cytokine Levels In Patients Research Articles

Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia--significance for activation of the kynurenine pathway.

Accumulating evidence indicates that schizophrenia is associated with brain immune activation. While a number of reports suggest increased cytokine levels in patients with schizophrenia, many of these studies have been limited by their focus on peripheral cytokines or confounded by various antipsychotic treatments. Here, well-characterized patients with schizophrenia, all receiving olanzapine treatment, and healthy volunteers were analyzed with regard to cerebrospinal fluid (CSF) levels of cytokines. We correlated the CSF cytokine levels to previously analyzed metabolites of the kynurenine (KYN) pathway. We analyzed the CSF from patients and controls using electrochemiluminescence detection with regard to cytokines. Cell culture media from human cortical astrocytes were analyzed for KYN and kynurenic acid (KYNA) using high-pressure liquid chromatography or liquid chromatography/mass spectrometry. We included 23 patients and 37 controls in our study. Patients with schizophrenia had increased CSF levels of interleukin (IL)-6 compared with healthy volunteers. In patients, we also observed a positive correlation between IL-6 and the tryptophan:KYNA ratio, indicating that IL-6 activates the KYN pathway. In line with this, application of IL-6 to cultured human astrocytes increased cell medium concentration of KYNA. The CSF samples had been frozen and thawed twice before analysis of cytokines. Median age differed between patients and controls. When appropriate, all present analyses were adjusted for age. We have shown that IL-6, KYN and KYNA are elevated in patients with chronic schizophrenia, strengthening the idea of brain immune activation in patients with this disease. Our concurrent cell culture and clinical findings suggest that IL-6 induces the KYN pathway, leading to increased production of the N-methyl-D-aspartate receptor antagonist KYNA in patients with schizophrenia.

Oligoclonal bands and increased cytokine levels in idiopathic intracranial hypertension.

The pathogenesis of idiopathic intracranial hypertension (IIH) is currently unknown and there are speculations about the contribution of some immunologic factors. The aim of this study is to investigate the presence of oligoclonal bands (OCBs) and cerebrospinal fluid (CSF) and/or serum cytokine levels in patients with IIH. Patients fulfilling revised diagnostic criteria for IIH were included. Their demographic, clinical, ophthalmologic and laboratory features were examined. Serum and CSF samples were detected by isoelectric focusing and immunoblotting for OCBs. The samples of IIH patients and control groups were investigated by ELISA for cytokine levels. We detected OCBs in eight (30.77%) patients diagnosed with IIH. There were no other obvious clinical and laboratory differences of IIH profiles between the patients with and without OCBs, but frequency of vision loss was significantly higher in the group with OCBs in comparison to OCB negatives (p = 0.038). Patients with IIH had highly elevated TNF-α, IFN-γ, IL-4, IL-10, IL-12, IL-17 in their sera compared to patients with multiple sclerosis (MS) and healthy controls. Furthermore, all cytokines except TNF-α in the CSF were found significantly higher in IIH patients compared to MS controls. The presence of OCBs and elevated cytokine levels in IIH patients may support an immunologic background in the pathophysiological pathway of this disorder.

Effect of atorvastatin on plasma NT-proBNP and inflammatory cytokine expression in patients with heart failure.

The aim of this study was to explore the effect of atorvastatin intervention on plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and inflammatory cytokine levels in patients with heart failure (HF). One hundred and twenty-three HF patients were selected from our hospital and randomly divided into control (N = 61) and observation (N = 62) groups; the former received conventional treatment, while the latter were given conventional treatment combined with atorvastatin. Plasma NT-proBNP, inflammatory cytokines [high-sensitive C-reactive protein (hs-CRP), interleukin (IL)-6, IL-10] and cardiac function [left ventricular end-diastolic dimension (LVEDD), left ventricular ejection fraction (LVEF), end-diastolic maximum flow rate ratio (E/A)] were compared among groups. The effective rate of treating HF significantly increased after atorvastatin treatment. The plasma NT-proBNP, IL-6, IL-10, hs-CRP, and LVEDD levels significantly decreased (P < 0.05), while the LVEF and E/A levels significantly increased (P < 0.05) in the observation group compared to the control group and before intervention. The NT-proBNP and cytokine levels significantly differed among patients with different classes of heart function (P < 0.05); the NT-proBNP and cytokine levels increased with the severity of heart function. Pearson's correlation analysis revealed a negative correlation between the NT-proBNP and inflammatory cytokine levels and LVEF and E/A values, and a positive correlation between these factors and LVEDD (P < 0.05). In conclusion, atorvastatin significantly improves cardiac function; the mechanism atorvastatin action was related to the decrease in plasma NT-proBNP and inflammatory cytokine levels.

Cytokine Serum Levels as Potential Biological Markers for the Psychopathology in Schizophrenia

We discuss the role of immune system disturbance in schizophrenia and especially changes of serum levels of cytokines in patients with schizophrenia. The cytokines are essential to wide range of functions related to the defense of the organisms from infectious and environmental dangers. However it is not known whether cytokines influence the presentation of psychotic symptoms. Identification of changes in the serum level of certain cytokines and their correlation with distinct psychopathological symptoms may facilitate the identification of subgroups of patients who are likely to benefit from immunotherapy or anti-inflammatory therapy. Such patients may benefit from tailored immunotherapy designed for modulation of abnormal cytokine levels related to specific positive or negative symptoms of schizophrenia.

Effect of urinary protease inhibitor (ulinastatin) on cardiopulmonary bypass: a meta-analysis for China and Japan.

ObjectivesA meta-analysis was conducted to investigate the effects of ulinastatin treatment on adult patients undergoing cardiac surgery under cardiopulmonary bypass (CPB).MethodsSeven electronic databases were searched for reports of randomized, controlled trials conducted up to February 2014 in which patients undergoing cardiac surgery with CPB were administered ulinastatin in the perioperative period.ResultsFifty-two studies with 2025 patients were retained for analysis. The results showed that the ulinastatin can attenuate the plasma levels of pro-inflammatory cytokines and enhance the anti-inflammatory cytokine levels in patients undergoing cardiac surgery with CPB. Meanwhile, the ulinastatin had a significant beneficial effect on myocardial injury. The mean differences (MD) and 95% confidence intervals (95% CI) of biochemical markers were −63.54 (−79.36, −47.72) for lactate dehydrogenase, −224.99 (−304.83, −145.14) for creatine kinase, −8.75 (−14.23, −3.28) for creatine kinase-MB, and −0.14 (−0.20, −0.09] for troponin I (all P<0.01). However, neither hemodynamics nor cardiac function improved significantly, except that the MD and 95% CI of mean arterial pressure were 2.50 (0.19, 4.80) (P = 0.03). There were no statistically significant differences in the use of inotropes, postoperative bleeding, postoperative complications, the intensive care unit (ICU) stay, and the hospital stay; however, the frequency of auto resuscitation increased significantly (OR 1.98, 95%CI 1.19 to 3.30, P<0.01), the duration of intubation (MD −1.58, 95%CI −2.84 to −0.32, P<0.01) and the duration of mechanical ventilation (MD −3.29, 95%CI −4.41 to −2.17, P<0.01) shortened significantly in patients who were treated with ulinastatin.ConclusionsUlinastatin can reduce the plasma levels of pro-inflammatory cytokines and elevate anti-inflammatory cytokine in patients from China and Japan undergoing cardiac surgery with CPB. Ulinastatin treatment may have protective effects on myocardial injury, and can increase the frequency of auto resuscitation, shorten the duration of intubation and mechanical ventilation.

Serum Cytokine Profile in Patients with Septic Shock/Severe Sepsis and Thrombocytopenia

IntroductionSepsis is the result of an uncontrolled inflammatory response to various stimuli such as bacterial infections. Sepsis can be complicated by hemodynamic instability, multi-organ dysfunction and hematological abnormalities. Patients with severe sepsis usually develop thrombocytopenia due to various reasons, and the presence of thrombocytopenia is considered as a negative prognostic marker. The aim of the present study was to determine the cytokine profile in serum of patients with severe sepsis and thrombocytopenia.Patients and MethodsSerum cytokine profile was analyzed in a cohort of 112 consecutive patients with severe sepsis and/or septic shock treated in the intensive care unit (ICU) of our institute from October/2009 to September/2012. Patients were divided in two groups (A and B). Group A consisted of 43 patients with severe sepsis and thrombocytopenia (platelet count below 70X103/ìl), while group B consisted of 69 patients without thrombocytopenia. Patients with thrombocytopenia due to disseminated intravascular coagulation (DIC), suspected drug etiology, or due to any obvious etiology such as hematologic malignancy were excluded from our analysis. A cohort of 10 healthy volunteers served as control group.Serum levels of IFNã, IL-8, ICAM, VCAM, and SUPAR (soluble urokinase plasminogen activation receptor) were estimated by using Luminex xMAP technology. Statistical analyses were performed using NCSS software. The following variables were entered in a multiple logistic regression model: 1) age and sex, 2) active malignancy vs. not, 3) septic shock vs. severe sepsis, 4) APACHEII score, 5) SOFA score, 6) serum IFNã, ICAM, VCAM, IL-8, and SUPAR levels, and 7) platelet number. All parameters were estimated on day of admission.ResultsHospital Mortality: Overall 65 out of 112 patients died during their hospital stay. The overall hospital mortality was 58%. In multivariate analysis non-survivors had higher APACHE score (p=0.01) and had lower platelet counts (p<0.001) as compared with survivors.Plasma cytokine levels in patients with and without thrombocytopenia: Patients in group A had a different cytokine profile as compared with patients in group B. Serum levels of VCAM and IFNã were not different between group A and B. However, patients with sepsis and thrombocytopenia had statistically significantly higher serum levels of ICAM, IL-8 and SUPAR (p<0.0001) in comparison with patients with severe sepsis and normal PLT count.Predictive value of serum cytokine for thrombocytopenia: Serum levels of ICAM, IL-8, and SUPAR were good predictors of the presence of thrombocytopenia in patients with sepsis. The ROC curves of ICAM, IL-8, and SUPAR serum levels in predicting thrombocytopenia in patients with sepsis are shown in Figure 1. The AUCs were 0.785 (95% CI, 0.696 – 0.857, p<0.001), 0.729 (95% CI, 0.637 – 0.809, p<0.001), 0.789 (95% CI, 0.701 – 0.861, p<0.001) for ICAM, IL-8 and SUPAR levels respectively. However in multiple logistic regression analysis serum levels of ICAM was the most powerful predictor of thrombocytopenia.ConclusionThrombocytopenia is not an uncommon finding in patients with severe sepsis. Although DIC or drug reactions are well known causes of low PLT counts, the pathogenesis of thrombocytopenia in patients with sepsis remains poorly understood. High levels of ICAM, IL-8 and SUPAR are usually associated with severe endothelial dysfunction. In our study, we showed that patients with thrombocytopenia have a specific serum cytokine profile expression consistent with the presence of endothelial damage. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Aqueous Humor Cytokine Levels in Patients with Polypoidal Choroidal Vasculopathy and Neovascular Age-Related Macular Degeneration

Purpose: To investigate the possible roles of various cytokines or growth factors in the pathogenesis of exudative age-related macular degeneration (AMD) by comparing aqueous humor levels of 14 cytokines between eyes with polypoidal choroidal vasculopathy (PCV) and those with neovascular AMD. Methods: Forty eyes from 40 patients with treatment-naïve exudative AMD consisting of 18 eyes with neovascular AMD and 22 eyes with PCV were studied. Twenty eyes from 20 patients with no retinal pathology who underwent cataract surgery served as controls. Aqueous humor samples were collected just before intravitreal ranibizumab injection in 40 eyes with exudative AMD and before cataract surgery in 20 control eyes. Concentrations of 14 cytokines were determined by chemiluminescence-based ELISA: interleukin (IL)-1α, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, vascular endothelial growth factor (VEGF), monocyte chemoattractant protein 1, interferon-γ-inducible protein (IP)-10 and C-reactive protein (CRP). Results: After adjusting for gender, age and axial length, concentrations of CRP and IP-10 were significantly higher in eyes with neovascular AMD or PCV compared with control eyes (p < 0.05), and IP-10 levels were strongly associated with lesion size (p = 0.002). None of the 14 cytokines, including VEGF, were significantly different between eyes with neovascular AMD and those with PCV. Conclusion: Aqueous humor concentrations of CRP and IP-10 were elevated in eyes with PCV or neovascular AMD. IP-10 could be associated with the pathogenesis of neovascular AMD and PCV. © 2014 S. Karger AG, Basel

Does dexmedetomidine have a cardiac protective effect during non-cardiac surgery? A randomised controlled trial.

This study was designed to determine the effects of dexmedetomidine on perioperative myocardial injury by observing peripheral circulatory changes in response to tracheal intubation and extubation, myocardial enzyme levels, myocardial ischaemia improvements, cardiovascular adverse events and cytokines in patients with coronary heart disease (CHD) undergoing non-cardiac surgery. This study was a prospective, randomized, double-blind trial. Eighty patients having CHD were scheduled for elective hip-replacement surgery and randomly allocated to receive a loading dose of 1 μg/kg dexmedetomidine followed by a 0.2 μg/kg per h infusion (Dex group; n = 40) or normal saline (control group; n = 40). Systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, rate-pressure product and changes in ST-T segment on the electrocardiogram were recorded every 5 min during surgery. Serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), glycogen phosphorylase BB (GP-BB), interleukin (IL)-6 and tumour necrosis factor (TNF)-α protein levels were determined preoperatively, at the end of surgery and 12 and 24 h after surgery. The improvement rate of myocardial ischaemia was higher in the Dex than control group (87.5% vs 32.5%, respectively; P < 0.05). In addition, the Dex group had lower serum CK-MB, IL-6, cTnI and GP-BB concentrations than the control group (P < 0.05). There was no significance difference in TNF-α between the two groups (P > 0.05). Dexmedetomidine can reduce myocardial injury and cytokine levels in patients with CHD undergoing non-cardiac surgery.

Correlation between human tear cytokine levels and cellular corneal changes in patients with bacterial keratitis by in vivo confocal microscopy.

We investigated bilateral tear cytokine levels in patients with unilateral bacterial keratitis (BK) as associated with in vivo confocal microscopic (IVCM) alterations in corneal nerves and dendritiform immune cells (DCs). A total of 54 (13 BK, 13 contralateral, 28 healthy controls) tear samples was collected prospectively and analyzed by multiplex microbeads assay. The IVCM of the central cornea was performed on the same day, and assessed for corneal nerve and DC alterations. Interleukin-1β, IL-6, and IL-8 were significantly elevated only in affected eyes (66.6 ± 26.8, 7174 ± 2430, and 810 ± 315 ρg/mL, respectively; P = 0.04, P < 0.001, and P < 0.001, respectively), compared to healthy controls (13.0 ± 4.0, 171.8 ± 32.1, and 56.5 ± 33.8 ρg/mL). Levels of chemokine ligand 2 (CCL-2), IL-10, and IL-17a were elevated only in contralateral eyes (813 ± 478, 86.7 ± 38.3, and 3350 ± 881 ρg/mL, respectively; P = 0.02, P = 0.01, and P = 0.04, respectively), compared to controls (73.7 ± 25.3, 17.5 ± 4.9, and 1350 ± 337 ρg/mL). Triggering receptor expressed on myeloid cells (TREM)-1 was significantly elevated in affected (551 ± 231 ρg/mL, P = 0.02) and contralateral unaffected (545 ± 298 ρg/mL, P = 0.03) eyes compared to controls (31.3 ± 12.4 ρg/mL). The density of DCs was significantly increased in affected (226.9 ± 37.3 cells/mm(2), P < 0.001) and unaffected (122.3 ± 23.7 cells/mm(2), P < 0.001) eyes compared to controls (22.7 ± 5.9 cells/mm(2)). Sub-basal nerve density significantly decreased in affected (3337 ± 1615 μm/mm(2), P < 0.001) and contralateral (13,230 ± 1635 μm/mm(2), P < 0.001) eyes compared to controls (21,200 ± 545 μm/mm(2)). Levels of IL-1β, IL-6, and IL-8 were significantly correlated with DC density (R = 0.40, R = 0.55, and R = 0.31, all P < 0.02) and nerve density (R = -0.30, R = -0.53, and R = -0.39, all P < 0.01). Proinflammatory tear cytokines are elevated bilaterally in patients with unilateral BK, and are correlated strongly with alterations in DCs and nerve density as detected by IVCM.

P.4.f.004 Cytokine levels in patients with obsessive–compulsive disorder

P.4.f.004 Cytokine levels in patients with obsessive–compulsive disorder

Relationship between bone mineral density and immune inflammatory parameters in women with osteoporosis concurrent with coronary heart diseases

Low bone mineral density (BMD) is a risk factor of osteoporotic fractures. The RANKL–RANK–OPG system and some cytokines are known to play a role in the regulation of bone remodeling. Cytokines and osteoprotegerin (OPG) are able to affect the cardiovascular system. It is highly relevant to study the relationship between BMD and cytokine levels in patients with a concurrence of osteoporosis (OP) and coronary atherosclerosis. Objective: to estimate the relationship between BMD and the level of cytokines and OPG in women having OP comorbid with coronary heart disease (CHD). Subjects and methods. Sixty women (mean age 68.7±8.8 years) with OP comorbid with CHD (Group 1) were examined; a control group consisted of 38 patients (mean age 69.4±8.1 years) with isolated CHD (Group 2). BMD was measured in two regions: lumbar vertebrae (LI–IV) and proximal femur, by employing a DEXA densitometer (CHALLENGER, France). The serum levels of OPG, interleukin (IL) 1β, 4, 6, 8, 10, and tumor necrosis factor (TNF) α were determined by enzyme-linked immunosorbent assay (ELISA). Results. The women with comorbidity were observed to have elevated IL6, 8, TNF-α, IL4, 10, and OPG levels. There was a negative correlation between IL1, TNF-α, and IL8 levels and vertebral BMD; OPG, IL4, 6, 8, and TNF-α concentrations were inversely related to femoral neck BMD. The independent factor of lower BMD was IL6 in the femoral neck and IL1 in the lumbar vertebrae. The findings suggest that there is a relationship between elevated cytokine levels and lower BMD in women having OP comorbid with CHD.

Combined impact of hepatitis C virus genotype 1 and interleukin-6 and tumor necrosis factor-α polymorphisms on serum levels of pro-inflammatory cytokines in Brazilian HCV-infected patients

We investigated the association between hepatitis C virus (HCV) genotypes and host cytokine gene polymorphisms and serum cytokine levels in patients with chronic hepatitis C. Serum IL-6, TNF-α, IL-2, IFN-γ, IL-4, IL-10, and IL-17A levels were measured in 67 HCV patients (68.2% genotype 1 [G1]) and 47 healthy controls. The HCV patients had higher IL-6, IL-2, IFN-γ, IL-10, and IL-17A levels than the controls. HCV G1 patients had higher IL-2 and IFN-γ levels than G2 patients. The -174IL6G>C, -308TNFαG>A, and -1082IL10A>G variants were similarly distributed in both groups. However, HCV patients with the -174IL6GC variant had higher IL-2 and IFN-γ levels than patients with the GG and CC variants. Additionally, HCV patients with the -308TNFαGG genotype had higher IL-17A levels than patients with the AG genotype, whereas patients with the -1082IL10GG variant had higher IL-6 levels than patients with the AA and AG variants. A significant proportion of HCV patients had high levels of both IL-2 and IFN-γ. The subgroup of HCV patients with the G1/IL6CG/TNFαGG association displayed the highest proportions of high producers of IL-2 and IFN-γ whereas the subgroup with the G1/TNFαGG profile showed high proportions of high producers of IL-6 and IL-17A. HCV patients with other HCV/cytokine genotype associations showed no particular cytokine profile. Our results suggest that HCV genotype G1 and IL-6 and TNF-α polymorphisms have a clinically relevant influence on serum pro-inflammatory cytokine profile (IL-2 and IFN-γ) in HCV patients.

The levels of proinflammatory cytokines in blood serum of patients with juvenile idiopathic arthritis

IL-1, IL-6 and TNF-alpha is a typical example of a multifunctional cytokine that is involved in the immune response, hemopoiesis and inflammation. In 1999 published data on the levels of cytokines in patients with JRA. It is noted that the level of IL-6 higher in patients with systemic variant of the disease in the active phase. This study confirms that levels of IL-6 and TNF-alpha can be markers of disease activity.

Profile of intraocular immune mediators in patients with age-related macular degeneration and the effect of intravitreal bevacizumab injection.

To measure intraocular cytokine levels in patients with exudative age-related macular degeneration and analyze changes in the cytokine profile 2 days after intravitreal bevacizumab injection. This prospective case-control study enrolled 37 patients (37 eyes) with age-related macular degeneration including polypoidal choroidal vasculopathy. Twenty-eight age-matched patients (28 eyes) who underwent cataract surgery were used as controls. Undiluted aqueous humor samples were collected after intravitreal bevacizumab injection. Two days after intravitreal bevacizumab injection, cataract surgery was performed and undiluted aqueous humor samples were collected at the beginning of surgery (10 eyes). Twenty-three cytokines were measured using flow cytometry. P values were corrected in multiple comparisons using the conservative Bonferroni-Holm method. The level of significance was set at 0.0022 (0.05/23). At baseline, aqueous humor levels of vascular endothelial growth factor, angiogenin, interferon gamma-inducible protein (IP)-10, macrophage inflammatory protein (MIP)-1β, monokine induced by interferon γ (Mig), and monocyte chemotactic protein (MCP)-1 were significantly higher in the age-related macular degeneration group than in the control group (P < 0.0022). The result of exploratory multivariate analysis showed that elevated angiogenin level was an important factor that discriminates the two groups (P = 0.0004). Two days after intravitreal bevacizumab injection, vascular endothelial growth factor levels tended to be reduced (P = 0.049), whereas interleukin (IL)-6 and IL-8 levels increased significantly (P < 0.0022). Vascular endothelial growth factor and also angiogenin, IP-10, MCP-1, MIP-1β, and Mig may be related to the pathogenesis of age-related macular degeneration. Intravitreal bevacizumab injection increases inflammatory cytokine levels, suggesting the induction of an inflammatory process.

Insulin resistance and increased muscle cytokine levels in patients with mitochondrial myopathy.

Mitochondrial dysfunction has been proposed to cause insulin resistance and that might stimulate cytokine production. The objective of the study was to elucidate the association between mitochondrial myopathy, insulin sensitivity, and cytokine levels in muscle. This was an experimental, controlled study in outpatients. Eight overnight-fasted patients (P) with various inherited mitochondrial myopathies and eight healthy subjects (C) matched for sex, age, weight, height, and physical activity participated in the study. The intervention included a 120-minute hyperinsulinemic, euglycemic clamp. Another morning, microdialysis of both vastus lateralis muscles for 4 hours, including one-legged, knee extension exercise for 30 minutes, was performed. Glucose infusion rate during 90-120 minutes of insulin infusion was measured. Cytokine concentrations in dialysate were also measured. Muscle strength, percentage fat mass, and creatine kinase in plasma did not differ between groups. The maximal oxygen uptake was 21 ± 3 (SE) (P) and 36 ± 3(C) mL/kg·min (2P < .05). Basal insulin, C-peptide, and glucagon were higher in P (55 ± 10, 980 ± 92, and 102 ± 13 pM) than in C (36 ± 12, 712 ± 98, and 44 ± 10 pM) (two-sided significance testing [2P ]< .05). The homeostasis model assessment insulin sensitivity index and glucose infusion rate (6.8 ± 1.0 vs 9.4 ± 1.3 mg/min·kg) were lower, and free fatty acids and glycerol at 120 minutes were higher in P vs C (2P < .05). Dialysate concentrations of TNF-α, IL-6, IL-8, IL-10, and monocyte chemoattractant protein-1 were higher in P vs C (2P < .05). Dialysate concentrations of these cytokines and of IL-1 receptor antagonist increased during exercise (2P < .05), identically in P and C. No differences existed in plasma cytokine concentrations. In patients with a variety of mitochondrial myopathies, insulin sensitivity of muscle, adipose tissue, and pancreatic A cells is reduced, supporting that mitochondrial function influences insulin action. Furthermore, a local, low-grade inflammation of potential clinical importance exists in the muscle of these patients.

Selenium supplementation in patients undergoing hematopoietic stem cell transplantation: effects on pro-inflammatory cytokines levels

BackgroundPro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) play an important role in the development of hematopoietic stem cell transplantation (HSCT) complications. We explored the effect of Selenium as an antioxidant and anti-inflammatory agent on pro-inflammatory cytokines levels in HSCT candidates.FindingsPlasma concentrations of TNF-α, IL-1β and IL-6 were measured in 74 patients from a double-blind, randomized, placebo-controlled study. In both groups, there were 37 patients with median age of 32 years. Patients received oral Se tablets (200 mcg) or placebo twice daily beginning from the first day of high dose chemotherapy (HDC) through 14 days after HSCT. Cytokine levels were determined before starting HDC (prior to first dose of Se), 7 and 14 days after HSCT. Plasma levels of TNF-α were not significantly different between Se and control group (P = 0.13). IL-1 levels were similar between two groups (P = 0.88). No significant differences were detected in IL-6 levels between Se and control group (P = 0.96).ConclusionSelenium had no effect on pro-inflammatory cytokines levels in patients undergoing HSCT. It is likely that earlier initiation and/or larger doses of Se are required to affect inflammatory cytokines significantly.

Diet and proinflammatory cytokine levels in head and neck squamous cell carcinoma.

Proinflammatory cytokine levels may be associated with cancer stage, recurrence, and survival. The objective of this study was to determine whether cytokine levels were associated with dietary patterns and fat-soluble micronutrients in patients with previously untreated head and neck squamous cell carcinoma (HNSCC). This was a cross-sectional study of 160 patients with newly diagnosed HNSCC who completed pretreatment food frequency questionnaires (FFQs) and health surveys. Dietary patterns were derived from FFQs using principal component analysis. Pretreatment serum levels of the proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) were measured using an enzyme-linked immunosorbent assay, and serum carotenoid and tocopherol levels were measured by high-performance liquid chromatography. Multivariable ordinal logistic regression models examined associations between cytokines and quartiles of reported and serum dietary variables. Three dietary patterns emerged: whole foods, Western, and convenience foods. In multivariable analyses, higher whole foods pattern scores were significantly associated with lower levels of IL-6, TNF-α, and IFN-γ (P ≤ .001, P = .008, and P = .03, respectively). Significant inverse associations were reported between IL-6, TNF-α, and IFN-γ levels and quartiles of total reported carotenoid intake (P = .006, P = .04, and P = .04, respectively). There was an inverse association between IFN-γ levels and serum α-tocopherol levels (P = .03). Consuming a pretreatment diet rich in vegetables, fruit, fish, poultry, and whole grains may be associated with lower proinflammatory cytokine levels in patients with HNSCC.

Interleukins as markers of inflammation in malignant and benign thyroid disease.

Thyroid disorders, including thyroid cancer and autoimmune thyroid diseases, have been closely associated with inflammation. This study aims to investigate the role of inflammation in thyroid disease by assessing serum cytokine levels in patients with malignant and benign thyroid conditions. Serum levels of ten interleukins (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 and IL-13) were quantitatively determined in 20 patients with thyroid cancer, 38 patients with benign thyroid disease and 50 healthy controls by multiplex technology. Serum IL-1β, IL-2, IL-4, IL-5 and IL-6 levels were strongly associated with each other. IL-10 and IL-12 correlated with IL-1β, IL-5, IL-6, and with each other. Age was inversely correlated with serum levels of IL-2, IL-4 and IL-13. A positive correlation between T3 and IL-13 levels was also observed. Significantly higher levels of IL-6, IL-7, IL-10 and IL-13, as well as significantly lower levels of IL-8 were observed in patients with benign and malignant thyroid disease compared to controls. The combination of IL-13 and IL-8 in a two-marker panel was highly efficient in discriminating thyroid disorders (AUC 0.90). Malignant and benign thyroid conditions are associated with altered expression levels of interleukins, supporting the association between thyroid disease and underlying inflammatory processes.

Cytokine levels of the aqueous humour in central serous chorioretinopathy

BackgroundThis study aimed to investigate the levels of aqueous humour cytokines in the eyes of patients with central serous chorioretinopathy (CSC), who received an intravitreal injection of bevacizumab, and to evaluate the differences in cytokine levels between bevacizumab responders and non‐responders.MethodsAqueous humour samples were collected from 39 eyes of 39 patients with CSC and 25 eyes of 25 control patients undergoing cataract surgery and were analysed using Multiplex bead assays. We compared the cytokine levels in patients with CSC (responders and non‐responders) and control subjects. After intravitreal injections of bevacizumab in patients with CSC, we evaluated the changes in visual acuity and optical coherence tomographic parameters.ResultsSignificantly increased levels of interferon gamma‐induced protein (IP‐10) were detected in the aqueous humour of eyes from patients with CSC compared to controls (p = 0.036). Vascular endothelial growth factor (VEGF) levels were significantly higher in bevacizumab responders than in non‐responders (p = 0.021). The concentrations of the other cytokines investigated did not differ significantly between patients with CSC and control subjects or between responders and non‐responders.ConclusionThe results of the present study suggest that IP‐10 and VEGF may contribute to the pathogenesis of CSC. It is clear that intravitreal bevacizumab was helpful in some of the patients with CSC, who showed higher levels of VEGF in the aqueous humour. However, the true effect and the rationale of anti‐VEGF injection treatment in patients with CSC remain to be elucidated. Our results suggest that patients with CSC may be more susceptible to VEGF and/or other cytokines than the normal population.

Abstract 125: Inflammatory Markers Influence Microembolization in Patients Undergoing Carotid Interventions

INTRODUCTION: Despite the use of embolic protection and improvement in surgical technique for carotid interventions, perioperative cerebral microembolization is still relatively common. Susceptibility to microembolization is largely uncontrolled and the effects remain poorly understood. We hypothesized that inflammation may play a role in this process and sought to identify plasma markers predicting embolization in patients undergoing carotid interventions. METHODS: Patients scheduled for carotid interventions at an academic center were prospectively recruited to the study. MRI with diffusion-weighted imaging (DWI) was performed prior to and within 48 hours following the procedure and used to identify new cerebral microemboli. Blood samples were collected at the time of intervention prior to carotid interrogation (Pre) and at 24 hours following intervention (Post). Plasma was isolated and analyzed by a 27-plex Luminex assay. The assay was performed in triplicate and Significance Analysis of Microarrays (SAM) identified significant inflammatory markers. Mann-Whitney U tests were performed to further evaluate these findings. RESULTS: 71 male patients were included with an average age of 70 years; 38 underwent CAS and 33 underwent CEA. 59% of the cohort exhibited postoperative DWI lesions. Post plasma samples were collected for all patients, and Pre samples were collected for a cohort of 19 patients. We observed significantly lower levels of several cytokines in patients with procedure-related DWI lesions, particularly platelet-derived growth factor (PDGF) (150.8 vs 389.6pg/ml, p&lt;.001). Patients with more complex plaques were also observed to have lower levels of PDGF. For the cohort with both Pre and Post samples, there was a significantly greater decrease in PDGF for patients with DWI lesions compared to those who did not. (U=382, Z=-2.6, p=.008). CONCLUSIONS: Lower plasma levels of cytokines were observed in patients with procedure-related DWI lesions, suggesting that patients who illicit an inappropriate immune response may be more susceptible to procedure-related microembolization. Impaired PDGF response may indicate poor repair mechanism to injury. Further investigation is warranted.