Serum Levels Of TNF Research Articles

Expression Levels of Serum Hepcidin, IL-6 and TNF-? and Clinical Significance in Malignant Tumor Patients with Anemia of Chronic Disease

To explore the effect and possible mechanism of serum hepcidin on malignant tumor patients combined with anemia of chronic disease (ACD). ELISA method was used to measure the concentrations of serum hepcidin, interleukine-6 (IL-6), and tumor necrosis factor α (TNF-α) in 40 malignant tumor patients with ACD. Meanwhile, the concentrations of serum hepcidin, IL-6, and TNF-α in 20 malignant tumor patients without ACD were measured. The differences in above indices between the two groups were compared. Meanwhile, the correlations of hemoglobin (Hb) value with hepcidin, IL-6, and TNF-α in the anemia group were analyzed, and the correlations of hepcidin with IL-6 and TNF-α were analyzed. The serum hepcidin, IL-6 and TNF-α levels in the patients from the anemia group were higher than those in the non-anemia group, which were 49.48±18.38 ng/mL vs. 10.36±5.28 ng/mL, 11.79±4.11 pg/mL vs. 5.46±2.37 pg/mL, and 10.73±3.94 pg/mL vs. 6.48±3.26 pg/mL, respectively(P＜0.05). Besides, Hb value in the patients from the anemia group had negative correlations with serum hepcidin and IL-6 (r values were -0.739 and -0.379, and P＜0.05), but had no correlation with TNF-α (r=-0.213, P>0.05). The serum hepcidin in the patients from the anemia group had a positive correlation with IL-6 (r=0.377, P＜0.05), but had no correlation with TNF-α (r=0.268, P>0.05). Conclusion: Hepcidin plays a critical role in the ACD onset of malignant tumor, and may happen mainly under the participation of IL-6.

Fecal galectin-1 as a potential marker for colorectal cancer and disease severity

Background/Aim. Colorectal cancer (CRC) represents one of the most common cancers worldwide. CRC is frequently diagnosed at advanced stages with poor prognosis, indicating the need for new diagnostic and prognostic markers. The aim of this study was to determine systemic and fecal values of galectin- 1 (gal-1) and ratios between gal-1 and proinflammatory cytokines: tumor necrosis factor-alpha (TNF-?), interleukin-1 beta (IL-1?) and interferon gamma (IFN-?), in the patients with CRC and the relationship with clinicopathological aspects of the disease. Methods. The blood samples and feces liquid fraction of 58 patients with CRC were analyzed. The serum and fecal levels of TNF-?, IL-1? and IFN-? and gal-1 were measured using sensitive enzyme-linked immunosorbent assay (ELISA) kits. Results. The fecal level of gal-1 was increased in the CRC patients with higher nuclear grade and poor tumor tissue differentiation. The gal-1/TNF-? ratio in the serum and feces had a higher trend in the patients with the advanced tumor-nodemetastasis (TNM) stage as well as the detectable lymphatic and blood vessel invasion. The gal-1/TNF-? and gal-1/IFN-? ratios were increased in the serum of patients with presence of lung/liver metastasis or peritoneal carcinomatosis, while the enhanced gal-1/IL-1 ratio was detected only in the serum of patients with lung metastasis. A positive correlation between the gal-1 value in feces and histological differentiation of tumor and biomarkers alpha-fetoprotein (AFP) and cancer antigen- 19-9 (CA 19-9), respectively, was also observed. The fecal values of gal-1 higher than 13,708.29 pg/g presented a highly sensitive and specific marker for histological differentiation of tumor tissue. Conclusion. We believe that the predomination of gal-1 over pro-inflammatory cytokines TNF-?, IL-1? and IFN- ? in the patients with advanced and progressive CRC may implicate on an immunomodulatory role of gal-1 in the limiting ongoing proinflammatory processes. The fecal values of gal-1 can be used as a valuable marker for the severity of CRC.

Following Chemotherapy: Serum Cytokine (Tumor Necrosis Factor, Interleukin-2, Interleukin-11), Immunoglobulin, Complement, Vascular Endothelial Growth Factor Levels, and the Systemic Symptoms like Capillary Leak Syndrome.

Several problems such as myalgia, arthralgia, fever, dyspnea, generalized edema, and pleural effusion can occur in cancer patients following the chemotherapy, especially at the first cycle of the first chemotherapy treatment. Although it is assumed that some cytokines are associated with the development of these symptoms and signs, their pathophysiology has not been discovered completely yet. They are usually mild, but they may rarely progress to the severe stage of “Systemic Capillary Leak Syndrome” with a high mortality rate. The objective of this study was to investigate the association between the serum levels of interleukin-2 (IL-2), interleukin-11 (IL-11), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), and these symptoms and signs. A total of 44 cancer patients who had neither heart, lung, liver, renal, or thyroid disease were recruited into this study. Their symptoms and signs were examined and questioned before the first cycle of the first chemotherapy treatment and the 24 h after this chemotherapy. All participant’s serum samples were taken, and the VEGF, TNF, IL-2, and IL-11 levels were studied. There was no association between the chemotherapeutic drugs, and the symptoms and signs such as edema, dyspnea, coughing, and flu-like symptoms. There was a significant decrease in IL-11 levels in the other treatment group compared with the group receiving paclitaxel, docetaxel, gemcitabine, and vinorelbine in the first day following chemotherapy (P = .006). However, no relation was observed between the symptoms and signs, the response to the chemotherapy, and the serum levels of VEGF, TNF, IL-2, and IL-11. These symptoms and life-threatening syndrome have been a current topic between the clinicians. Although some drugs and mediators are accused, its pathophysiology has not been discovered completely yet. In this study, we could not detect any association between the symptoms, signs, and the cytokine levels following the chemotherapy.

Beneficial anti-inflammatory effects of combined rosuvastatin and cilostazol in a TNF-driven inflammatory model

Due to anti-inflammatory and anti-thrombotic functions, statins and antiplatelets are widely used for patients with cardiovascular-related or coronary artery diseases. Patients with systemic or complex diseases are commonly prescribed multiple targeted medications; thus, a proper combination of two or more drugs for beneficial efficacy is considered in clinical therapy. Recent studies have suggested that combinational therapy with statins and other medications accelerates their single effect to suppress inflammatory responses. However, the therapeutic efficacy and underlying mechanism of combination treatment with rosuvastatin and cilostazol have been poorly studied. Mice were administered rosuvastatin alone, cilostazol alone or rosuvastatin and cilostazol in combination, and then injected with LPS or TNF to induce acute inflammation. The serum TNF level, macrophage infiltration of the lesioned aortas and mice mortality were observed in the acute inflammation model. The phosphorylation of MAPK was analyzed in TNF-stimulated HeLa cells. Compared to the treatment with cilostazol alone, the combination treatment with rosuvastatin and cilostazol significantly reduced not only the levels of TNF in the sera but also macrophage infiltration in aortic lesions. In addition, the combination therapy decreased TNF-mediated phosphorylation of the MAPK signaling pathway and improved the survival rate in the TNF-driven inflammatory mice model. Rosuvastatin combined with cilostazol therapy can greatly improve the anti-inflammatory effect of monotherapies, resulting in reduced mortality of mice; thus, we propose the potential of use of this combination therapy as anti-TNF agent.

Genetic and pharmacological validation of TAK1 inhibition in macrophages as a therapeutic strategy to effectively inhibit TNF secretion

Immune challenge of invading macrophages at sites of infection is associated with release of TNF, which triggers a local cytokine storm as part of the normal inflammatory response. Whereas this response maybe beneficial in fighting off infections, similar responses triggered in autoimmune diseases contribute significantly to the underlying damaging pathology associated with these diseases. Here we show that Takinib, a highly discriminatory inhibitor of transforming growth factor Beta- activated kinase 1 (TAK1), selectively and potently reduces TNF production in pro-inflammatory THP-1 macrophages. A complete survey of 110 cytokines, showed robust loss of proinflammatory cytokine responsiveness to lipopolysaccharide (LPS) and interferon gamma (IFNγ) challenge in response to Takinib. The mechanisms of action of Takinib was recapitulated in TAK1 KO macrophages. TAK1 KO cells showed significant loss of TNF production as well as release of IL-6 in response to LPS challenge. Furthermore, Takinib blocked the ability of exogenously added LPS to promote phosphorylation of, c-Jun, p38 protein kinases as well as downstream transcription factors regulated by nuclear factor κ-light-chain-enhancer of activated B cells (NFκB). In a mouse LPS challenge model, Takinib significantly reduced TNF serum levels. Our findings demonstrate that Takinib has utility in the treatment inflammatory disease by locally suppressing TNF production from invading macrophages.

Exercise activates vagal induction of dopamine and attenuates systemic inflammation

Physical exercise is one of the most important factors improving quality of life, but it is not feasible for patients with morbidity or limited mobility. Most previous studies focused on high-intensity or long-term exercise that causes metabolic stress or physiological adaption, respectively. Here, we studied how moderate-intensity swimming affects systemic inflammation in 6–8 week old C57BL/6J male mice during endotoxemia. One-hour swimming prevented hypokalemia, hypocalcemia, attenuated serum levels of inflammatory cytokines, increased anti-inflammatory cytokines but affected neither IL6 nor glycemia before or after the endotoxic challenge. Exercise attenuated serum TNF levels by inhibiting its production in the spleen through a mechanism mediated by the subdiaphragmatic vagus nerve but independent of the splenic nerve. Exercise increased serum levels of dopamine, and adrenalectomy prevented the potential of exercise to induce dopamine and to attenuate serum TNF levels. Dopaminergic agonist type-1, fenoldopam, inhibited TNF production in splenocytes. Conversely, dopaminergic antagonist type-1, butaclamol, attenuated exercise control of serum TNF levels. These results suggest that vagal induction of dopamine may contribute to the anti-inflammatory potential of physical exercise.

Factors of depression among patients with rheumatoid arthritis.

ObjectivesThe aim of this study was to assess the correlation between symptoms of depression and the course and clinical picture of rheumatoid arthritis (RA).Material and methods120 patients with RA were included in the study: 104 (87%) female patients and 16 (13%) male patients. All studied patients completed the following questionnaires: Beck Depression Inventory (BDI), Ford Insomnia Response to Stress Test (FIRST), Athens Insomnia Scale (AIS) and Health Assessment Questionnaire (HAQ). The serum levels of IL-1β, TNF-α, and IL-6 were measured using standard ELISA assays at the time of the first questionnaire assessment.ResultsSymptoms of depression were found in 91 patients (76%), including 79 (87%) women and 12 (13%) men. There were no significant differences between the prevalence of depression in women and men (p = 0.93). Symptoms of depression occurred more often in patients who were professionally inactive, compared with the professionally active patients (p = 0.04). Significant correlations was demonstrated between the value of BDI and the patient’s pain assessed by the visual analogue scale (VAS) value (r = 0.36), the disease activity assessed by the patient and the physician evaluated in millimetres on the VAS scale (r = 0.38 and r = 0.30, respectively), the number of painful and swollen joints (r = 0.22 and r = 0.26, respectively), DAS28 (r = 0.31) as well as the Health Assessment Questionnaire (HAQ) value (r = 0.46). Longer duration of the disease was observed in patients with symptoms of depression (p = 0.02). Also a significant difference in the assessment of BDI between patients treated with biological drugs and those receiving no such treatment was observed (p = 0.042).ConclusionsProfessional inactivity and longer disease duration are important factors influencing symptoms of depression in patients with RA. Higher values of HAQ increase the probability of the occurrence of depression symptoms. The use of biological drugs that reduce the level of proinflammatory cytokines may have a positive effect on reducing the severity of depressive symptoms.

Preliminary study showing no association between G238A (rs361525) tumor necrosis factor-\u03b1 (TNF-\u03b1) gene polymorphism and its serum level, hormonal and biochemical aspects of polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is the main cause of female infertility. Interactions among genetic, biochemical, and immunological factors can affect the pathogenesis of PCOS. As a proinflammatory cytokine, tumor necrosis factor-α (TNF-α) plays an important role in this regard. The present study aimed to evaluate the association of the rs361525 gene single-nucleotide polymorphism (SNP) and TNF-α serum levels with the hormonal and biochemical characteristics of PCOS in Iranian individuals.MethodsThe SNP rs361525 in the TNF-α gene was analyzed by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) in a total of 111 PCOS patients and 105 healthy females. Serum levels of TNF-α, lipid and hormone profiles, and biochemical factors were measured using enzyme-linked immunosorbent assay (ELISA) and calorimetric methods, as appropriate.ResultsThe TNF-α serum level was higher in women with PCOS compared with the control group (p < 0.0001), and it was significantly correlated with the homeostasis model assessment (HOMA) factor (r = 0.138, p < 0.05). No significant differences were found in the genotype and allelic frequencies between the two groups (p > 0.05). Higher levels and significant differences were found for the HOMA factor, luteinizing hormone/follicle-stimulating hormone (LH/FSH), testosterone, and body mass index (BMI) in the PCOS group compared with the control group (p < 0.0001). High LH/FSH ratios (odds ratio [OR] = 1.98, 95% confidence interval [CI] = 1.20–3.28, p < 0.01), and high HOMA factor (OR = 5.04, 95% CI = 2.82–9.01, p < 0.001) were significantly associated with an increased risk of PCOS.ConclusionsDespite the lack of significant difference between rs361525 polymorphism of the TNF-α gene and PCOS, the serum level of TNF-α was increased in PCOS patients and positively correlated with the HOMA factor. Elevation of the LH/FSH ratio and HOMA for insulin resistance (HOMA-IR) increased the risk of PCOS. Therefore, TNF-α could indirectly contribute to PCOS progression.

Effect of tumor necrosis factor-\u03b1 on the expression of the ammonia transporter Rhcg in the brain in mice with acute liver failure

BackgroundAmmonia and tumor necrosis factor-alpha (TNF-α) play important roles in the mechanisms of hepatic encephalopathy (HE). Rhesus glycoprotein C (Rhcg) is important for ammonia transport especially in the kidney. The aim of the present study was to investigate the role of Rhcg in the brain in acute liver failure (ALF) and the effect of TNF-α on Rhcg expression.MethodsALF mouse models were generated by treatment with d-galactosamine (D-GalN) and lipopolysaccharide (LPS), or D-GalN and TNF-α. ALF induction was blocked by pretreatment with anti-TNF-α IgG. The levels of serum TNF-α were determined by ELISA. Blood ammonia and brain ammonia concentrations were detected using an ammonia assay kit. The expression and distribution of Rhcg in the brain tissues of ALF mice were examined by western blotting, real-time PCR, immunohistochemical, and immunofluorescence analyses.ResultsSerum TNF-α levels were increased in the LPS/D-GalN group. Blood and brain ammonia were increased in the LPS/D-GalN- and TNF-α/D-GalN-induced ALF groups. Rhcg mRNA and protein levels were elevated in both ALF groups, consistent with the increase in blood and brain ammonia. Rhcg was mainly expressed in vascular endothelial cells and astrocytes. Pretreatment with anti-TNF-α IgG antibody downregulated Rhcg in brain tissues in the LPS/D-GalN group, prevented the occurrence of ALF, and reduced blood and brain ammonia levels in the LPS/D-GalN group.ConclusionTNF-α promoted the transport of ammonia from the blood to brain tissues and exacerbated the toxic effects of ammonia by upregulating Rhcg.

Combination of Salvia miltiorrhiza and ligustrazine attenuates bleomycin-induced pulmonary fibrosis in rats via modulating TNF-\u03b1 and TGF-\u03b2

BackgroundIdiopathic pulmonary fibrosis (IPF), a chronic, progressive, fibrosing interstitial lung disease, is associated with extremely poor prognosis, and lacks effective treatment. The frequently used immunosuppressive therapies such as dexamethasone (DEX) are often associated with side effects. Recently, combination of two Chinese herbal medicine preparations, Salvia miltiorrhiza and ligustrazine (SML), serves as an alternative medicine for treatment of IPF in clinical practices in China. The aim of this study is to compare the anti-fibrotic effect of SML with that of DEX and to investigate the underlying mechanisms.MethodsA rat model of bleomycin (BLM) induced pulmonary fibrosis was used in this study. Ninety rats were assigned to six groups: control group; BLM-group; BLM and dexamethasone group (BLM + DEX); BLM + low-dose SML; BLM + medium-dose SML and BLM + high-dose SML. Rats were sacrificed on day 7, 14 and 28 after treatment. The extent of alveolitis and fibrosis was observed by H&E and Masson’s trichrome staining. The expressions of TNF-α, TGF-β1 and SMAD4 were determined and quantified by immunohistochemical analysis. The serum levels of TNF-α and TGF-β1 were further quantified by ELISA kits.ResultsBoth DEX and SML treatment attenuated BLM-induced lung injury and pathological collagen deposition in rats, showing improved alveolitis and fibrosis scores on day 7, 14, 28, compared to the BLM group (p < 0.05). The anti-fibrotic effect of SML was in a dose-dependent manner, and the medium- and high-dose SML showed comparable effect with DEX on day 14 and 28. Expressions of TNF-α, TGF-β1 and SMAD4 were significantly decreased in the DEX- and SML-treated groups compared with BLM groups (p < 0.05). Medium- and high-dose SML showed better repression of TNF-α, TGF-β1 and SMAD4 expression compared to DEX at all time points (p < 0.05). Notably, SML at different dosages did not affect serum levels of alanine aminotransferase, aspartate aminotransferase and creatinine.ConclusionsSML is safe and effective in repressing BLM-induced pulmonary fibrosis, which might be through modulating the expression of TNF-α and TGF-β1. Our findings advocate the use of SML for IPF, which might serve as a better treatment option over DEX.

Immunosuppression Induced by Perioperative Peritonitis Promotes Lung Metastasis.

Perioperative intra-abdominal infection has been reported as a risk factor for metastasis. The aim of this study was to investigate the mechanism by which peritonitis induces immunosuppression in the lung, which in turn promotes lung metastasis. C57BL/6 mice were intravenously administered B16F10 melanoma cells to induce lung metastasis and subsequently subjected to cecal ligation and puncture (CLP) to induce peritonitis or sham surgery. The number of lung metastatic nodules was evaluated. Cell fractions in lungs and serum cytokines after CLP were investigated. CLP mice showed an increased number of lung metastases compared to sham-treated mice. The fraction and number of natural killer (NK) cells in lungs of CLP mice were significantly reduced in early post-CLP phase. Myeloid-derived suppressor cells (MDSCs) in lungs were significantly decreased in CLP mice. Serum IL-6 and TNF levels were significantly elevated in CLP mice. Peritonitis promoted lung metastasis in a murine model, which may be attributable to the impact of NK cells and MDSCs in the lungs.

Effect of artemisinin and neurectomy of pterygoid canal in ovalbumin-induced allergic rhinitis mouse model

BackgroundAllergic rhinitis (AR), characterized by sneezing, nasal itching and rhinorrhea, affects a large number of population. This study aimed to explore the effects of artemisinin alone or combined with neurectomy of pterygoid canal in ovalbumin-induced AR mouse model and illustrate the underlying mechanisms.MethodsAllergic symptoms were evaluated to verify inhibitory effect of artemisinin alone or combined with neurectomy of pterygoid canal on AR. Serum levels of histamine, immunoglobulin E (IgE) and inflammatory factors TNF, INF-γ, IL-1β IL-10, IL-4 and IL-5 were measured by ELISA. The mRNA levels of TNF, INF-γ, IL-1β and IL-10 in local lymph nodes were measured by RT-qPCR. The total and phosphorylated levels of ERK and JNK were assessed by Western blot. CD4+CD25+Foxp3+ T (Treg) cells were analyzed by flow cytometry.ResultsArtemisinin significantly relieved the behavior symptoms of AR mice. The administration of artemisinin strikingly suppressed the expression of histamine, IgE and inflammatory factors. An increased Treg cell proportion and inhibited ERK phosphorylation were observed in artemisinin-treated groups as compared to those in the AR group. Moreover, artemisinin plus neurectomy of pterygoid almost abolished the behavioral score increase in AR mice.ConclusionsThese results indicated that artemisinin exhibited anti-allergic effect by inhibiting ERK activation and increasing Treg cell proportion, which subsequently decreased the expressions of allergic mediators. In addition, artemisinin combined with neurectomy of pterygoid showed better efficacy than artemisinin alone.

Cholinergic signaling in the dorsal motor nucleus regulates systemic inflammatory responses via the vagus nerve

Abstract The autonomic nervous system regulates organ homeostasis via neural reflex circuits. The inflammatory reflex is the prototypical neural circuit composed of afferent and efferent fibers that travel via the vagus nerve to regulate TNF production. Previous studies have demonstrated that stimulation of the cervical vagus nerve attenuates serum TNF levels and cytokine production in the spleen, but efferent vagus nerve neurons originate both in the dorsal motor nucleus of the vagus (DMV) and in the nucleus ambiguus (NA) in the brainstem. The origin of the specific fibers that regulate splenic TNF production was previously unknown. Here, we selectively stimulated cholinergic neurons in the DMV and measured TNF in endotoxemic mice. A fiber-optic cannula was inserted under stereotactic guidance into the DMV in transgenic mice expressing channelrhodopsin under the choline acetyltransferase promoter. Animals were subjected to either optogenetic stimulation (n=15) or no light (sham control, n=15) for five minutes (473nm laser, 20Hz, 25% duty cycle). After 24 hours, animals were challenged with intraperitoneal lipopolysaccharide (0.25mg/kg), and serum collected after 90 min. Optogenetic stimulation but not sham stimulation of the cholinergic neurons in the DMV significantly attenuated endotoxin-induced serum TNF levels. Additionally, direct neural recording of splenic nerve activity during optogenetic stimulation of the DMV revealed that signals originating in the brainstem travel via the vagus nerve to the spleen. Together these studies provide new insights into the identity and central origin of the efferent vagus nerve fibers regulating TNF production during endotoxemia.

Transient Receptor Potential Ankyrin 1 Mediates the Afferent Arm of the Inflammatory Reflex

Abstract The vagus nerve plays an important role in maintaining an organism’s immune homeostasis through the inflammatory reflex. Inflammatory molecules including LPS, TNF and IL-1β can mediate electrophysiological changes in vagus nerve signaling. Reasoning that these signals are mediated though specific neuronal fibers that can be identified by molecular markers, we administered endotoxin to mice that received optovin, a molecule that interacts with TRPA1 and is light sensitive. Selective stimulation of vagus nerve TRPA1+ fibers significantly reduce serum TNF levels (sham: 920.9 ± 87.9 pg/ml vs. stimulated: 456.8 ± 69.4 pg/ml). This reduction is ablated by proximal vagotomy, indicating that the signals are afferent in nature. Prior work suggests that the afferent vagus nerve is required for IL-1β induced febrile responses and sickness behavior. Here we administered IL-1β to TRPA1 KO mice and observed that body temperature was maintained as compared to wildtype (peak temperature change; wildtype: −2.35 ± 0.15 °C vs. TRPA1 KO:0.18 ± 0.40 °C). When recording electrical activity from the VN, IL-1β induces a significant increase in VN activity in WT mice. However, no significant increase is observed in TRPA1 KOs. Cecal ligation and puncture in TRPA1 KOs caused significantly higher disease severity scores, percent weight loss, and mortality. These results identify TRPA1 as both a marker for fiber specific inflammatory signaling as well as a necessary component for regulating inflammatory homeostasis.

Diverse expression of TNF-\u03b1 and CCL27 in serum and blister of Stevens\u2013Johnson syndrome/toxic epidermal necrolysis

BackgroundThe pathogenesis of Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is not fully understood. Our previous study reported that chemokine CCL27 was overexpressed in serum of SJS/TEN patients. The objective of this study was to investigate the levels of CCL27 and TNF-α in serum and blister fluid from patients with SJS/TEN during the acute stage or resolution phase.MethodsA total of 27 patients with SJS/TEN and 39 healthy donors were recruited to the study. Serum and vesicular levels of CCL27 and TNF-α were determined by enzyme-linked immunosorbent assays.ResultsSerum levels of CCL27 and TNF-α were significantly elevated in patients with SJS/TEN during the acute stage as compared to the resolution phase and also compared with levels observed in normal controls (P = 0.001/< 0.001; P = 0.012/< 0.001). Serum TNF-α levels were significantly higher in patients with SJS/TEN during the resolution phase compared with normal controls (P < 0.001). Serum CCL27 levels were positively correlated with TNF-α levels during the acute stage (rs = 0.660; P < 0.001). Blister fluid exhibited much lower CCL27 levels than serum did during the acute stage (P = 0.008). TNF-α levels were much higher in vesicles in contrast to serum from acute stage (P = 0.040) as well as serum from resolution phase (P = 0.029).ConclusionsOur study demonstrated roles of CCL27 and TNF-α in promoting the course of SJS/TEN. CCL27 may act early in the course of disease, via the circulation, whereas TNF-α acts throughout the course of disease, in skin lesions.

Efficacy of sequential dialysis combined with hydroxyethyl starch in the treatment of refractory edema of nephrotic syndrome

Objective To observe the efficacy of sequential dialysis combined with hydroxyethyl starch in the treatment of patients with refractory edema of nephrotic syndrome. Methods Eighty-eight patients with refractory edema of nephrotic syndrome were randomly divided into control group (n=44) and combination group (n=44) according to the digital table.The control group was treated with hydroxyethyl starch, and the combination group was treated with sequential dialysis combined with hydroxyethyl starch.The levels of urinary NAG, urinary KIM-1 and serum ICAM-1, TNF-, IL-6 were compared.And the clinical efficacy of the two groups was evaluated. Results The improvement time of clinical symptoms in the observation group was significantly shorter than that in the control group, and the average weight loss of the observation group was significantly higher than that of the control group(t=7.099, 9.279, all P 0.05). Compared with before treatment, 24h urine of the two groups after treatment was increased (tcombination group=36.266, P 0.05). After treatment, the serum levels of ICAM-1, TNF- and IL-1β in the combination group were significantly lower than those before treatment and those in the control group(tcombination group=15.655, 16.882, 16.091, all P 0.05). Conclusion Sequential dialysis combined with hydroxyethyl starch in the treatment of refractory edema of nephrotic syndrome can improve the clinical curative effect and improve the renal function of patients.It is worthy to be further promoted. Key words: Sequential dialysis; Hydroxyethyl starch; Nephrotic syndrome, refractory edema

Cytokine profile as diagnostic and prognostic factor in neonatal sepsis

Antecedents: The serum levels of some cytokines can be useful in the diagnosis of neonatal sepsis; the prognostic value of a cytokine profile has not, to our knowledge, been explored in this disease.Objective: The objective of this study is to evaluate the diagnostic value of the serum levels of cytokines IL-1, -2, -4, -5, -6, -7, -8, -10, -12, -13, and -17, TNF, IFNγ, G-CSF, GM-CSF, MCP1, and MIP1β in neonates with high risk of developing sepsis.Methods: Sepsis was evaluated in 96 high-risk neonates. We assessed cytokine levels on hospital admission and during or not during sepsis.Results: Fifty (52%) presented sepsis (26 early and 24 late). Sepsis was associated with high levels of IL-6, IL-10, G-CSF, and MCP1 and low levels of IFNγ, early sepsis with high levels of IL-6 and G-CSF, severe sepsis with high levels of IL-6 and IL-10, while deaths or sequelae was associated with low levels of IL-4, IL-12, IFNγ, and high levels of GM-CSF. IL-6 values of ≥40.1 pg/mL were associated with the development of any type of sepsis (relative risk [RR]: 1.70; 95% confidence interval [95% CI]: 1.18–2.24; p = .01), while IL-6 values of ≥44.9 pg/mL were associated with early sepsis (RR: 1.29; 95% CI: 1.29–4.56; p = .01).Conclusion: In neonates with high risk for the development of sepsis, there is an association between levels of IL-6, IL-10, and G-SCF and the disease development/outcome.

Effects of rosuvastatin (added to hypocaloric diet) on serum periostin, adiponectin, proinflammtory cytokines levels and hepatic steatosis in non-alcoholic fatty liver disease patients with dyslipidemia

ObjectiveNon-alcoholic fatty liver disease (NAFLD) is strongly associated with dyslipidemia. Rosuvastatin exhibits greater efficacy in the treatment of dyslipidemia as compared to other statins, so we aimed to explore its effect on NAFLD patients. MethodsWe conducted a prospective observational study (6-month) to evaluate NAFLD patients with dyslipidemia receiving rosuvastatin with hypocaloric diet (N=81) or hypocaloric diet alone (N=114). Using propensity score matching, patients (N=76) were divided into two equal groups. Serum levels of periostin, adiponectin, TNF α and IL-6 were determined using ELISA kits; hepatic steatosis was evaluated by ultrasound; hepatic fibrosis was assessed by NAFLD fibrosis and BARD scores at 0 and 6 months, and liver enzymes were assessed at 0, 2, 4, 6 months of study treatment. ResultsRosuvastatin, in addition to hypocaloric diet diminished hepatic steatosis (p=0.011); decreased serum periostin (p=0.003), TNF α (p=0.012), IL-6 levels (p=0.010); increased serum adiponectin levels (p=0.028), and improved NFS, BARD scores (p>0.05). Alteration in grades of hepatic steatosis were found significantly correlated with change in serum levels of periostin (rs=0.256, p=0.025) and adiponectin (rs=0.282, p=0.014), while association was insignificant with the changes in serum TNF-α (rs=0.148, p=0.202) and IL-6 levels (rs=0.127, p=0.274). ConclusionTreatment with rosuvastatin, in addition to the hypocaloric diet, resulted in a significant decrease in serum periostin levels; ameliorated grades of hepatic steatosis and fibrosis scores, indicating that rosuvastatin, in addition to hypocaloric diet may be effective treatment for NAFLD with dyslipidemia.

Anti-Inflammatory and Antioxidant Properties of Black Mulberry (Morus nigra L.) in a Model of LPS-Induced Sepsis.

Sepsis is a complex disease and is the cause of many deaths worldwide. Sepsis pathogenesis involves a dysregulated inflammatory response with consequent production of inflammatory mediators and reactive species. The production and excessive release of these substances into the systemic circulation trigger various cellular and metabolic alterations that are observed during the disease evolution. Thus, more studies have been carried out to investigate the therapeutic potential of plants such as Morus nigra L., popularly known as black mulberry. Studies have shown that plants belonging to the Morus genus are rich in secondary metabolites such as flavonoids which are associated with important biological activities as antioxidant and anti-inflammatory actions. Based on this context, the objective of our study was to evaluate the anti-inflammatory and antioxidant properties of Morus nigra L. in a sepsis model induced by LPS. Male C57BL/6 mice were distributed in four groups: control, sepsis, sepsis treated with leaf extract of mulberry, and sepsis treated with mulberry pulp. The animals were treated with 100 μL of their respective treatments for twenty-one days. Sepsis was induced at the 21st day with lipopolysaccharide (LPS) by intraperitoneal injection. The animals were euthanized 24 hours after receiving the LPS injection. The data obtained were analyzed in GraphPad Prism 6.0 software. Our results showed that treatment with either extract significantly decreased the number of leukocytes in the bronchoalveolar lavage fluid and serum levels of TNF in septic animals. Regarding the redox status, the treatments significantly decreased the antioxidant activity of the enzyme glutathione peroxidase. Regarding metalloproteinase type 2, it was observed that the treatment with black mulberry pulp was able to significantly reduce the activity of this enzyme concerning the sepsis group. Finally, these results together promoted an increase in the animal's survival that received the black mulberry leaf or pulp extract.

Effects of melatonin treatment on the spermatogenesis and serum inflammatory cytokine levels in diabetic rats

Aim: Diabetes mellitus (DM) is known to have side effects on sexual and reproductive functions in males. The aim of current study was to investigate the effect of melatonin treatment on spermatogenesis and serum inflammatory cytokine levels in diabetic rats. Material and Method: Eighteen adult Wistar albino male rats were divided randomly into three groups each containing 6 rats; control group (group 1), diabetic group (group 2), diabetic treated with melatonin group (group 3). Experimental diabetes was obtained by administrating 50 mg/kg streptozotocin. Melatonin treatment was administered intraperitoneally for 7 days at a dose of 20 mg, daily. Serum levels of interleukin-1 beta (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were assayed. Spermatogenesis was evaluated according to Johnsen score at immunopathological examination.Results: The Johnsen scores in control, diabetic and treatment groups were 9.78, 8.91, and 9.61, respectively. Spermatogenesis was negatively affected in diabetic rats and significantly improved with melatonin therapy (p0.05). The serum levels of TNF-α in diabetic rats were observed to be increased compared to the control group (p0.05). The levels of serum IL-1β and TNF- α were significantly decreased with melatonin treatment. IL-6 levels were not different among the three groups (p=0.248). Conclusions: In the present study, intraperitoneal melatonin treatment was determined to have a positive effect of on spermatogenesis and caused a decrease in serum inflammatory cytokine levels in diabetic rats.Keywords: Cytokines; Diabetes Mellitus; Melatonin; Rats; Spermatogenesis.