Increased annexin-V and decreased TNF-α serum levels in chronic-medicated patients with schizophrenia

Schizophrenia (SZ) is a chronic severe mental disorder. Increased inflammatory processes have been shown in acute and chronic SZ. Apoptotic processes may alter the neuronal network and are involved in the pathogenesis of several neurodegenerative diseases, such as SZ. Annexin-V seems to have a role on inhibition of pro-inflammatory activities during apoptosis. Tumor necrosis factor (TNF-alpha) is a cytokine involved in systemic inflammation and is a member of a group of cytokines which stimulate acute phase reactions. A chronic immune activation in SZ has been shown. The aim of this study was to compare annexin-V and TNF-alpha serum levels in chronic medicated patients with SZ and healthy controls. Thirty-eight outpatients from the HCPA Schizophrenia Program and 38 healthy controls were enrolled to this study protocol. Annexin-V and TNF-alpha serum levels were measured with ELISA. Serum annexin-V levels were significantly higher in patients with SZ than in controls (p < 0.001) and TNF-alpha significantly lower (p < 0.001). The present result of increased annexin-V and decreased serum levels of TNF-alpha compared to controls may be a result of the stabilization phase of psychosis and a reduction in metabolic brain aggression. In this complex picture, increased levels of annexin-V and decreased levels of TNF-alpha in our sample would be explained by illness stability and chronic treatment. Our findings support the hypothesis of a state dependant process of inflammation in SZ. Further prospective studies to clarify the findings described in this paper are needed.     

Evaluation of serum levels of IL-6, TNF-α, IL-10, IL-2 and IL-4 in patients with chronic hepatitis

Background

Changes in various cytokine activities have been reported during both HBV and HCV infections, while an imbalance of pro-inflammatory and anti-inflammatory cytokine production influences their immunopathogenesis. The aims of the present study are (a) to measure serum levels of interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), interleukin-10 (IL-10), interleukin-2 (IL-2) and interleukin-4 (IL-4) in a sample of patients affected either by chronic HBV infection or by chronic HCV infection and in healthy controls (b) to correlate serum levels of IL-6, TNF-α, IL-10, IL-2 and IL-4 with biochemical markers of liver disease and (c) to evaluate differences of the aforementioned cytokines between HBV and HCV patients, as well as between patients and healthy controls.

Methods

The study population consisted of 50 patients with chronic hepatitis B, 40 patients with chronic hepatitis C and 30 healthy controls aged between 28 and 75 years. Biochemical markers of liver disease were evaluated by routine methods approved by IFCC. Serum concentrations of IL-6, TNF-α, IL-10, IL-2 and IL-4 were determined with the Human Cytokine/Chemokine Panel I Merck Millipore.

Results

HBV patients showed statistically significant difference in TNF-α and IL-2 levels, versus healthy controls. HCV patients showed statistically significant difference in TNF-α, IL-10 and IL-2 levels versus healthy controls. IL10 and IL-2 levels were significantly different between HBV and HCV patients.

Conclusions

This study evaluated the serum cytokine levels (IL-6, TNF-α, IL-10, IL-2 and IL-4) of chronic hepatitis B or C patients, as well as the differences in such levels between patients and healthy controls. Correlations of cytokine levels with biochemical markers of liver disease were also observed, reflecting the degree of activity of the inflammatory process in the liver.     

Elevated IL-1α and CXCL10 serum levels occur in patients with homozygous sickle cell disease and a history of acute splenic sequestration

Acute splenic sequestration (ASS) and chronic hypersplenism are common features of homozygous sickle cell (SS) disease in the first 5 years of life affecting one-third of subjects in the Jamaican Cohort Study. The risk factors are largely unknown and the current study explores a possible role of genetic factors. We have explored these in subjects who received splenectomy in the management of ASS (n=8) or chronic hypersplenism (n=9) along with age, gender, and genotype matched controls using Luminex Technology to assess 42 human cytokines/chemokines, including IL-1α and CXCL10 (IP-10). Levels of IL-1α (p=0.008) and CXCL10 (p=0.009) were significantly elevated in patients treated by splenectomy compared with the control group. Levels of IL-1α were significantly higher in those with a history of ASS compared with matched normal controls (p=0.028) but not in those treated for hypersplenism (p=0.093). Furthermore, several significant differences were found in the median ratios of some cytokine biomarkers between the splenectomized group and the normal controls. These observations are consistent with acute splenic sequestration having a distinct phenotype which may be helpful in predicting those at risk of this complication and suggest that the mechanism of these differences merit further study.     

TNF-α-308G/A polymorphism associated with TNF-α protein expression in patients with diabetic nephropathy

Aims: This study was to clarify the regulated effects of TNF-α -308G/A polymorphism on TNF-α and investigate the relationship of -308G/A polymorphisms with diabetic nephropathy (DN) susceptibility. Methods: 86 DN patients and 94 healthy individuals were enrolled in our study. Polymerase chain reaction-sequence specific primer (PCR-SSP) detection technology was used to testify single nucleotide polymorphism (SNP) of TNF-α gene. Enzyme-linked immunosorbent assay (ELISA) was used to measure the content of TNF-α protein. Odds ratio (OR) with 95% CI were used to evaluate the association of TNF-α -308G/A polymorphism and DN susceptibility. Results: The level of TNF-α protein was much higher in DN patients compared to that of controls (P < 0.05). For TNF-α -308G/A, G/A genotype could increase the risk for DN (OR = 2.15, 95% CI = 1.08-4.30). Moreover, a allele frequency was found higher in cases compared with controls, which suggested that A allele served as an genetic-susceptibility factor for DN (OR = 1.89, 95% CI = 1.10-3.26). Further analysis indicated that level of TNF-α for individuals with mutant genotype (GA and AA) were higher than that of individuals with wild genotype (P < 0.05). However, AA genotype showed no effects on DN susceptibility (OR = 2.08, 95% CI = 0.56-7.33). Conclusion: TNF-α-308G/A polymorphism was associated with expression level of TNF-α and served as an genetic-susceptibility factor for DN.     

B cells produce less IL-10, IL-6 and TNF-α in myasthenia gravis

Abstract

B cells from myasthenia gravis (MG) patients with autoantibodies (Aab) against acetylcholine receptor (AChR), muscle-specific kinase (MuSK) or with no detectable Aab were investigated as cytokine producing cells in this study. B cells were evaluated for memory phenotypes and expressions of IL-10, IL-6 and IL-12A. Induced productions of IL-10, IL-6, IL-12p40, TNF-α and LT from isolated B cells in vitro were measured by immunoassays. MG patients receiving immunosuppressive treatment had higher proportions of memory B cells compared with healthy controls and untreated patients. With CD40 stimulation MG patients produced significantly lower levels of IL-10, IL-6. With CD40 and B cell receptor stimulation of B cells, TNF-α production also decreased in addition to these cytokines. The lower levels of these cytokine productions were not related to treatment. Our results confirm a disturbance of B cell subpopulations in MG subgroups on immunosuppressive treatment. B cell derived IL-10, IL-6 and TNF-α are down-regulated in MG, irrespective of different antibody productions. Ineffective cytokine production by B cells may be a susceptibility factor in dysregulation of autoimmune Aab production.     

IL-1α and IL-6 predict vascular events or death in patients with cerebral small vessel disease—Data from the SHEF-CSVD study

PurposeThe natural clinical course of cerebral small vessel disease (CSVD) was not thoroughly described. The aim of this single center cohort study was to establish biochemical predictors of vascular events and death in CSVD patients during a 24-month follow-up.Patients and methodsA total of 130 functionally independent patients with marked MRI features of CSVD and recent lacunar stroke (n = 52,LS), vascular Parkinsonism (n = 28,VaP) or dementia (n = 50,VaD) were prospectively recruited. Serum markers of endothelial dysfunction, inflammation and hemostasis were determined at baseline. The primary outcome was defined as occurrence of death or any vascular events during the observation.ResultsThe mean age was 72 ± 8.1 years, and 37.6% of the patients were women. The mean follow-up time was 22.3 ± 4.3 months, and 84.6% of patients had extensive white matter lesions on baseline MRI. The overall mortality rate was 6.9%, and vascular events or death occurred in 27% of the patients. Kaplan-Meier survival curves revealed no significant differences between CSVD groups (log rank p = 0.49). Cox regression analysis revealed that IL-1α (HR 1.4; 95%CI 1.09–1.8), IL-6 (1.4;1.1–2.2), hs-CRP (1.1;1.06–1.9), homocysteine (1.4;1.1–1.8), fibrinogen (1.4;1.05–2), and d-dimer (2.7;1.6–4.5) were significantly associated with the primary outcome. IL-1α (1.3;1.07–1.8), IL-6 (1.4;1.02–2.2), d-dimer (2.8;1.6–5) and homocysteine (1.4;1.1–1.8) remained significant after adjusting for age, sex and CSVD radiological markers.ConclusionsOur study demonstrated the important prognostic role of various circulation markers of inflammation in individuals with different clinical signs and radiological markers of CSVD. The strongest association occurred between IL-1α, IL-6 and recurrent stroke, other vascular events and death.     

Expression of IL-10 and TNF-α in Rats with Cerebral Infarction after Transplantation with Mesenchymal Stem Cells

We investigated the effects of bone marrow-derived mesenchymal stem cells （MSCs） transplantation on the recovery of neurological functions in rat＇s MCAO （middle cerebral artery occlusion） model and its mechanism. MSCs were isolated from bone marrow of male Sprague Dawley （SD） rats. Female adult SD rats were randomly assigned into 4 groups： sham-operated group, MCAO group, vehicle group and MCAO ＋ MSCs-treated group. MSCs were injected into the lateral ventricle of rats in the MSCs-treated group and the same volume of PBS was given to the vehicle group. The expressions of IL-10 and TNF-α were assayed by RT-PCR and ELISA detections at day 1 and 4 after MCAO. The infarction volume was measured by TTC-staining. All rats underwent behavioral tests before, as well as 1, 4, and 14 days after MCAO. MSCs significantly improved functional recovery compared with the control at day 14 after transplantation. Compared with the MCAO group and the vehicle group, the expression of IL-10 mRNA and its protein level in the MSCs group significantly upregulated. However, the expression of TNF-α at day 4 after MCAO in the MSCs group significantly decreased compared with that of the MCAO group and the vehicle group. As a result, transplantation with MSCs significantly decreased infarct volume at day 1 and 4. This study strongly suggested transplantation with MSCs could reduce neuronal injury post focal cerebral ischemia in rats partly by regulating the expressions of IL-10 and TNF-α in the brain.     

Clinical and serological manifestations associated with interferon-α levels in childhood-onset systemic lupus erythematosus

OBJECTIVE:

To determine the serum levels of interferon alpha in childhood-onset systemic lupus erythematosus patients, their first-degree relatives and healthy controls and to evaluate the associations between serum interferon alpha and disease activity, laboratory findings and treatment features.

METHODS:

We screened consecutive childhood-onset systemic lupus erythematosus patients in a longitudinal cohort at the pediatric rheumatology unit of the State University of Campinas between 2009 and 2010. All patients demonstrated disease onset before the age of 16. Disease status was assessed according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Interferon alpha levels were measured using an enzyme-linked immunoabsorbent assay.

RESULTS:

We included 57 childhood-onset systemic lupus erythematosus patients (mean age 17.33±4.50), 64 first-degree relatives (mean age 39.95±5.66), and 57 healthy (mean age 19.30±4.97) controls. Serum interferon alpha levels were significantly increased in childhood-onset systemic lupus erythematosus patients compared to their first-degree relatives and healthy controls. Interferon alpha levels were significantly increased in patients with positive dsDNA antibodies, patients with cutaneous vasculitis, patients with new malar rash and patients who were not receiving medication. Interferon alpha levels correlated with C3 levels and systemic lupus erythematosus Disease Activity Index scores. In addition, we observed an inverse correlation between patient age and interferon alpha levels.

CONCLUSION:

Interferon alpha may play a role in the pathogenesis of childhood-onset systemic lupus erythematosus, especially in cutaneous manifestations and dsDNA antibody formation. The observation that interferon alpha levels are increased in patients who are not taking medication should be investigated in longitudinal studies to determine whether elevated interferon alpha levels may predict systemic lupus erythematosus flares.     

Concentration levels of IL-10 and TNFα cytokines in patients with human papilloma virus (HPV) DNA+ and DNA− cervical lesions

The present study was performed to assess the immune response in women with human papilloma virus (HPV) DNA⁺ and DNA^? cervical lesions. Eighty women with cervical lesions (age range?=?25–70 years) and 20 healthy individuals (control group) were enrolled in the study. Lesions were cytologically classified into four groups: ASC-US (20), CINI (30), CINII-III (16), and cervical carcinoma (14) prior to HPV DNA detection. Estimation of interleukin (IL)-10 and tumor necrosis factor (TNF)-α levels in cervical secretions and serum of the studied patients was performed utilizing ELISA. PCR screening kits were used to detect HPV DNA in cervical smears obtained from the studied cases with the different lesions. IL-10 levels in cervical secretions of HPV DNA⁺ were significantly greater than those from DNA^? patients (i.e., 88.73 vs 24.00 pg/ml) and from controls (i.e., 88.73 vs 8.27 pg/ml) and the levels were higher in DNA^? patients than in controls (i.e., 24.00 vs 8.27 pg/ml). In comparison, serum IL-10 levels in these patients did not significantly differ from control values (i.e., 13.69 vs 12.16 vs 9.99 pg/ml, respectively). TNFα levels in cervical secretions of the HPV DNA⁺ and DNA^? cases did not significantly differ from values for the controls (i.e., 12.18 vs 9.90 vs 7.90 pg/ml, respectively). Serum TNFα of these patients also did not differ significantly from controls (i.e., 11.59 vs 11.90 vs 10.83 pg/ml, respectively). The detected levels of IL-10 in cervical secretions of patients with HPV DNA⁺ lesions was significantly higher than in their sera, while secretion TNFα levels were nominally greater than sera values. Lastly, higher levels of IL-10 were observed in secretions of 10–14 (71.4%) patients who had progressive cervical lesions (HSIL and cervical cancer stages) who were HPV DNA⁺ than observed in 20 of 66 (30.0%) of DNA^? patients with similar progressive lesions. In general, the higher levels of IL-10 than of TNFα suggested a potential down-modulation of tumor-specific immune responses to HPV-infected lesions. This phenomenon appears to provide a tumor ‘progressive’ microenvironment in these particular patients.     

Concentration levels of IL-10 and TNFα cytokines in patients with human papilloma virus (HPV) DNA⁺ and DNA⁻ cervical lesions

The present study was performed to assess the immune response in women with human papilloma virus (HPV) DNA? and DNA? cervical lesions. Eighty women with cervical lesions (age range?=?25-70 years) and 20 healthy individuals (control group) were enrolled in the study. Lesions were cytologically classified into four groups: ASC-US (20), CINI (30), CINII-III (16), and cervical carcinoma (14) prior to HPV DNA detection. Estimation of interleukin (IL)-10 and tumor necrosis factor (TNF)-α levels in cervical secretions and serum of the studied patients was performed utilizing ELISA. PCR screening kits were used to detect HPV DNA in cervical smears obtained from the studied cases with the different lesions. IL-10 levels in cervical secretions of HPV DNA? were significantly greater than those from DNA? patients (i.e., 88.73 vs 24.00 pg/ml) and from controls (i.e., 88.73 vs 8.27 pg/ml) and the levels were higher in DNA? patients than in controls (i.e., 24.00 vs 8.27 pg/ml). In comparison, serum IL-10 levels in these patients did not significantly differ from control values (i.e., 13.69 vs 12.16 vs 9.99 pg/ml, respectively). TNFα levels in cervical secretions of the HPV DNA? and DNA? cases did not significantly differ from values for the controls (i.e., 12.18 vs 9.90 vs 7.90 pg/ml, respectively). Serum TNFα of these patients also did not differ significantly from controls (i.e., 11.59 vs 11.90 vs 10.83 pg/ml, respectively). The detected levels of IL-10 in cervical secretions of patients with HPV DNA? lesions was significantly higher than in their sera, while secretion TNFα levels were nominally greater than sera values. Lastly, higher levels of IL-10 were observed in secretions of 10-14 (71.4%) patients who had progressive cervical lesions (HSIL and cervical cancer stages) who were HPV DNA? than observed in 20 of 66 (30.0%) of DNA? patients with similar progressive lesions. In general, the higher levels of IL-10 than of TNFα suggested a potential down-modulation of tumor-specific immune responses to HPV-infected lesions. This phenomenon appears to provide a tumor 'progressive' microenvironment in these particular patients.     

Protective effect of Ulinastatin against murine models of sepsis: Inhibition of TNF-α and IL-6 and augmentation of IL-10 and IL-13

AimExcessive production of inflammatory mediators during invasive infection plays a key role in the pathogenesis of sepsis. In an attempt to improve survival of patients with this lethal syndrome, agents were developed to selectively inhibit mediators in this inflammatory response. Ulinastatin (UTI), a human protease inhibitor, inhibits the enhanced production of pro-inflammatory molecules. However, it is unknown if Ulinastatin treatment could result in protective effects for sepsis. The aim of this study was to investigate the role of Ulinastatin on septic rats.MethodsSixty male Wistar rats were divided into six groups, 10 of each: sham-operation plus PBS (5 ml), cecal ligation and puncture (CLP) plus PBS (5 ml), CLP plus UTI (5000 U/kg), CLP plus UTI (10,000 U/kg), CLP plus UTI (20,000 U/kg) and sham-operation plus UTI (10,000 U/kg). Rats in the UTI groups after CLP operation were treated with Ulinastatin by intraperitoneal injection at different doses and then compared with untreated sepsis control animals.ResultsThe intestinal concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-13 (IL-13) were significantly higher in septic rats than those in normal rats. Ulinastatin administration effectively suppressed the levels of TNF-α and IL-6, whereas it markedly enhanced the levels of IL-10 and IL-13.ConclusionUlinastatin may possess a protective role in the septic process by inhibiting TNF-α and IL-6, and augmenting IL-10 and IL-13 concentrations in intestine of septic rats.     

Influence of Maternal Hyperglycemia on IL-10 and TNF-α Production: The Relationship with Perinatal Outcomes

Aims

This study was conducted to evaluate maternal and placental concentrations of interleukin 10 (IL-10) and tumor necrosis factor-alpha (TNF-α) in pregnant women with glycemic mean (GM) < or ≥100 mg/dL, as well as correlate IL-10 and TNF-α placental concentrations with perinatal outcomes.

Methods

One hundred eighty-six pregnant women were distributed in groups determined by a GM <100 mg/dL or a GM ≥100 mg/dL. The GM, HbA1c levels, maternal and placental concentrations of IL-10 and TNF-α, and the correlation of placental cytokines with perinatal outcomes were evaluated.

Results

In maternal blood, the lowest concentrations of IL-10 (p?=?0.0019) and TNF-α (p?=?0.0185) were observed in the GM ≥100-mg/dL group. The placentas from GM ≥100 mg/dL group exhibited higher TNF-α concentrations (p?=?0.0385). Placental IL-10 directly correlated with hemoglobin (r?=?0.63; p?=?0.02) and insulin (r?=?0.78; p?=?0.01) levels in the umbilical cord and with 1-min (r?=?0.53; p?=?0.0095) and 5-min (r?=?0.69; p?=?0.0003) Apgar scores. Placental TNF-α displayed a tendency to inversely correlate with fetal weight (r?=??0.41; p?=?0.05).

Conclusion

Compared to GM <100 mg/dL, GM ≥100 mg/dL was associated with a reduction in maternal IL-10 and TNF-α concentrations and increased placental TNF-α production. Placental IL-10 production was similar in both groups studied and directly correlated with hemoglobin and umbilical cord insulin levels, as well as with the 1- and 5-min Apgar scores.     

IL-15 that a regulator of TNF-α in patients with diabetes mellitus type 2

Diabetes mellitus type 2 (DM2), obesity, and the metabolic syndrome are considered that a low-grade chronic inflammatory condition. Although synthesis of different pro- and anti-inflammatory cytokines has been implicated in this process, this low-grade inflammatory condition is characterized especially by an increase in Tumor Necrosis Factor alpha (TNF-α), a cytokine that has been associated to the development of insulin resistance and muscle wasting in the diabetic patients. In consequence, mechanisms implicated in attenuating the deleterious effects of TNF-α are activated. One of these mechanisms may involve interleukin 15 (IL-15), which has proven effect on intermediate metabolisms, regulating blood glucose and lipid levels, and diminishing proteolysis in striated muscle. This suggests that the induction of endogenous IL-15 production by a simple event as physical activity may aid in decreasing or even inhibiting the negative effects of TNF-α in patient with DM2 or obesity, in which a low grade chronic inflammatory condition is present.     

Association of miR-155, miR-187 and Inflammatory Cytokines IL-6, IL-10 and TNF-α in Chronic Opium Abusers

Inflammation - Substance use disorders are known to be associated with inflammation. However, the dynamics of inflammatory cytokines and microRNA in chronic opium use is yet unexplored. The current...     

Serum levels and genetic variation of IL-35 are associated with multiple sclerosis: a population-based case–control study

This study aimed to investigate the association between serum levels and polymorphic variants of IL-35 with susceptibility, clinical features, and disease severity in multiple sclerosis (MS) patients.

This case–control study recruited 186 MS patients and 195 sex- and age-matched healthy controls. Serum levels and polymorphic variants of IL-35 were determined by ELISA and restriction fragment length polymorphism (RFLP)-PCR or high resolution melting (HRM) analysis methods, respectively. In addition, by in silico analysis, we evaluated the location and function of the polymorphism.

Serum levels of IL-35 were significantly lower in the patients than those of healthy controls (49.3?±?3.7 vs. 69.5?±?7.8, p?=?0.009). EBI3 rs4740 polymorphism of IL-35 was associated with 2.2-fold increased risk of MS susceptibility (95% CI, 1.3–3.9, p?=?0.005). However, there were no differences in the genotype distribution and allele frequencies of IL-35 rs568408 between the patients and controls (p?>?0.05). In silico results showed that variation in IL-12A and EBI3 may affect on protein pathways of the cells and different components of the immune system such as NF-κB and INF-γ.

The results show that IL-35 polymorphisms might be a genetic risk factor for the development of MS.

     

Relationship between serum levels of IL-18 and IgG1 in patients with primary Sjögren's syndrome, rheumatoid arthritis and healthy controls

Primary Sjögren's syndrome (SS) is characterized by inflammation in salivary and lachrymal glands, with a local predominance of Th1‐like cytokines, as well as the pleiotropic cytokine interleukin (IL) 18. High serum levels of polyclonal IgG are common, with a subclass imbalance in which IgG1 is increased and IgG2 is normal or low. IL‐18 is also of pathogenetic importance in rheumatoid arthritis. In the present study we looked for any relationship between serum IL‐18 as well as transforming growth factor (TGF) β1 versus IgA, IgM, and IgG subclass levels in SS (n = 16), rheumatoid arthritis (RA) (n = 15), and healthy controls (n = 15). SS was defined by the revised American‐European classification criteria. IL‐18 and TGF‐β1 were analyzed with enzyme immunoassays (EIA), and IgG1, IgG2 and IgG3 by single radial immunodiffusion. In the composite group of RA, SS and normal controls, IgG1 and IL‐18 were related (R = 0·52, P = 0·0005). No relation was found neither between IL‐18 versus IgG2, IgG3 or IgA, nor between serum TGF‐β1 versus any of the immunoglobulins. Since serum levels of IL‐18 are related to serum IgG1, IL‐18 may be of importance for IgG1 switch and/or release.     

Why do some cancer patients with depression desire an early death and others do not?

Major depression is a well-documented risk factor for suicide in cancer patients as well as in the general population. However, there are no data explaining why some cancer patients suffering from major depression have suicidal ideation, while others do not. The authors investigated the background differences among cancer patients suffering from major depression with and without suicidal ideation by analyzing the consultation data of patients referred to the psychiatry division. Among the 1,721 referred patients, 220 (12.8%) were diagnosed with major depression, and of these 113 (51.4%) had suicidal ideation. Logistic regression analysis indicated that poor physical functioning and severe depression were significant risk factors. These preliminary findings suggest that the severity of major depression and physical functioning are important indicators of suicidal ideation among cancer patients.