Blood Levels Of IL-6 Research Articles

Advantage of a Narrow Spectrum Host Defense (Antimicrobial) Peptide Over a Broad Spectrum Analog in Preclinical Drug Development.

The APO-type proline-arginine-rich host defense peptides exhibit potent in vitro killing parameters against Enterobacteriaceae but not to other bacteria. Because of the excellent in vivo properties against systemic and local infections, attempts are regularly made to further improve the activity spectrum. A C-terminal hydrazide analog of the Chex1-Arg20 amide (ARV-1502) shows somewhat improved minimal inhibitory concentration against Moraxellaceae. Here we compared the activity of the two peptides as well as an inactive dimeric reverse amide analog in a systemic Acinetobacter baumannii infection. Only the narrow spectrum amide derivative reduced the 6-h blood bacterial burden by >2 log10 units reaching statistical significance (p = 0.03 at 5 mg/kg and 0.031 at 2 mg/kg administered intramuscularly). The hydrazide derivative, probably due to stronger activity on cell membranes, lysed erythrocytes at lower concentrations, and caused toxic effects at lower doses (10 mg/kg vs. 25 mg/kg). In a limited study, the amide induced a >5-fold production of the anti-inflammatory cytokine IL-10 over untreated naïve mice and minor increases in the anti-inflammatory IL-4 and pro-inflammatory cytokines TNF-α and IL-6, in blood. The blood of hydrazide-treated mice exhibited significantly lowered levels of IL-10 and slightly decreased IL-4 and TNF-α. These results suggest that the improved efficacy of the narrow-spectrum amide analog is likely associated with increased anti-inflammatory cytokine production and better stimulation of the immune system. Although blood IL-6 and TNF-α levels are frequently used as markers of potential toxicity in drug development, we did not observe any notable increase in mice receiving the toxic polyamide antibiotic colistin.

Effect of early fluid resuscitation combined with low dose cyclophosphamide on intestinal barrier function in severe sepsis rats.

To investigate the effect of early fluid resuscitation on intestinal microecology in rats with severe sepsis. The severe sepsis model used was mainly cecal ligation perforation (CLP) model. Male SD rats were randomly divided into five groups: sham, CLP, CLP + normal saline (NS), CLP + cyclophosphamide (CTX), and CLP + NS + CTX. (1) The levels of IL-6, IL-10, and TNF-α in peripheral blood were measured by ELISA. (2) The expression of occludin/β-action in colonic tissue of mice was examined by Western Blot. (3) The intestinal permeability was measured by FD70 detection. (4) The length of the chorionic membrane was measured by colon histopathological staining. (5) The intestinal epithelial cell apoptosis was measured with the apoptosis index. (1) The rat model of severe sepsis was successfully replicated, and the 7-day survival rate of sepsis mice in each group was analyzed. (2) The expression level of splenic junction protein and the pathological damage in colonic tissue of the severe sepsis mice was significantly different between sham, CLP, CTX, NS, and NS + CTX (P < 0.05). The expression of tight junction protein in the NS + CTX mice was the highest, and the pathological damage was the smallest. (3) The colonic tissue apoptosis and intestinal permeability in the severe sepsis mice were compared with those of the colon tissues (P < 0.05). (4) The expression levels of IL-6, IL-10, and TNF-α in peripheral blood were significantly increased after severe sepsis (P < 0.01). The expression of IL-6 and TNF-alpha in each treatment group decreased (P < 0.05), while the expression of IL-10 in NS + CTX group increased significantly (P < 0.01). (1) We successfully replicated the rat model of severe sepsis. (2) Early fluid intervention and cyclophosphamide treatment can significantly improve the 7-day survival rate of the sepsis mice. (3) The fluid resuscitation and cyclophosphamide can delay intestinal damage to the intestinal tract barrier function and play a protective role.

The effects of bisphenol A on some plasma cytokine levels and distribution of CD8+ and CD4+ T lymphocytes in spleen, ileal Peyer’s patch and bronchus associated lymphoid tissue in rats

The effects of bisphenol A on the some plasma cytokine levels and distribution of CD8+ and CD4+ T lymphocytes in spleen, ilealPeyer’s patch and bronchus-associated lymphoid tissue in rats were investigated. A total of fourty male Wistar Albino rats were divided into five groups including 8 rats in each one: control, vehicle, BPA 5, BPA 50 and BPA 500 groups. Doses of 5, 50 and 500 μg/kg BPA were dissolved in ethanol, then mixed with corn oil. The control group received no treatment. The vehicle group was given the ethanol-corn oil mixture. BPA 5, BPA 50 and BPA 500 groups were given, respectively, 5, 50, and 500 μg/kg/day orally. In blood samples, IL-4, IL-6, IL-10 and TNF-α plasma levels were determined with ELISA. Tissue samples (spleen, ileal Peyer’s patches and lung) were processed by means of routine histological techniques. CD4 and CD8 were stained immunohistochemically. Data obtained from this study showed that, BPA causes the alteration on immune parameters including cytokine profile, distribution of CD8+ and CD4+ T lymhpocytes in spleen and ileal Peyer’s patches. Present study indicated that BPA may affect immune systems even at lower doses.Disruption of immun system cells and cytokine levels can result in harmful outcomes triggering autoimmune diseases and immunodeficiencies.

Combined Effect of NF-κB Inhibitor and β2-Adrenoreceptor Agonist on Mouse Mortality and Blood Concentration of Proinflammatory Cytokines in Sepsis.

Experiments on random-bred albino mice showed that NF-κB inhibitor (BAY 11-7082) and β2-adrenoreceptor agonist (dexmedetomidine hydrochloride) significantly reduced mouse mortality in 4 and 24 h after sepsis modeling (intraperitoneal administration of E. coli) by reducing blood levels of proinflammatory cytokines TNFα, IL-1β, and IL-6. The combined administration of NF-κB inhibitor and β2-adrenoreceptors agonist have an additive effect.

IL-17 blood levels increase in healthy pregnancy but not in spontaneous abortion.

Cytokines are essential to maintain and coordinate the correct activity of immune cells during human pregnancy. IL-17 is a pro-inflammatory cytokine that induces the expression of many inflammatory mediators. The aim of this study was to compare the levels of Th1, Th2 and Th17 cytokines of women ongoing normal pregnancy with those found in women who suffered spontaneous abortion. IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ peripheral blood levels were measured in women who suffered spontaneous abortion (n = 13, blood collected up to 24h after abortion), and were compared with healthy successful pregnancies (n = 16). Cytokine levels were measured using a cytometric bead array (CBA analysis). Similar cytokine levels were observed between spontaneous abortion and healthy pregnant women excepted to IL-17, which levels were increased in the healthy pregnant women (p = 0.0232). Our results show high IL-17 levels in the peripheral blood of women at late stages of healthy pregnancy, although low IL-17 levels were detected in the peripheral blood of women just after spontaneous abortion. In line with recent studies, this finding highlights IL-17 as a regulatory cytokine essential to the maintenance of a successful pregnancy.

Xuebijing injection induces anti-inflammatory-like effects and downregulates the expression of TLR4 and NF-κB in lung injury caused by dichlorvos poisoning

BackgroundThe mechanism in lung injury caused by acute organophosphate pesticide poisoning (AOPP) and an effective treatment remains unclear. We aim to clarify how the inflammatory lung injury caused by AOPP might be modulated by Xuebijing (XBJ) injection. MethodsAOPP-induced lung injury model was induced by dichlorvos (DDVP) subcutaneous administration in rats and XBJ injection was administered by intraperitoneal injection after DDVP challenge. The effects of XBJ injection were assessed by lung histopathological analysis and lung injury scores, lung wet-to-dry weight ratios (WDR) and oxygenation, differential immune cell count in bronchoalveolar lavage fluid (BALF), IL-6 and TNF-α levels in blood, the levels of TLR4 and NF-κB proteins in lung tissue and blood acetylcholinesterase (AChE) activity. ResultsDDVP administration resulted in damage of lung histopathology and lower PaO2/FiO2 ratios (P < 0.05), which were notably attenuated by XBJ injection (P < 0.05). Total cell, macrophage, and neutrophils count in BALF and TNF-α and IL-6 levels in blood were significantly increased after DDVP exposure (P < 0.05), which were notably ameliorated by XBJ injection (P < 0.05). TLR4 and NF-κB protein in lung tissue expression after DDVP challenge were markedly increased (P < 0.05), and they were substantially downregulated by XBJ injection (P < 0.05). In addition, blood AChE activity was significantly decreased by DDVP administration (P < 0.05), however, there was no significant improvement after XBJ injection. ConclusionXBJ injection prevents DDVP poisoning induced lung injury by attenuating the inflammatory response. The protective effect appears to be mediated through downregulation of the TLR4 and NF-κB expression.

Effect of montelukast on the expression of CD4+CD25+ regulatory T cells in children with acute bronchial asthma.

The aim of this study was to investigate the effect of montelukast on the expression of CD4+CD25+ regulatory T cells in children with acute bronchial asthma. Fifty-six child patients with acute bronchial asthma treated in the Department of Pneumology at the Shangluo Central Hospital were selected and randomly divided into the control group (n=28) and treatment group (n=28). The control group was treated with the conventional therapy of bronchial asthma, while the treatment group received montelukast on the basis of the control group for 7 days. The clinical symptoms, lung function and proportion of CD4+CD25+ regulatory T cells in peripheral T lymphocyte subsets in patients in the two groups were observed. Moreover, the levels of inflammatory factors and immunoglobulin E (IgE) in peripheral blood in both groups were detected. The effective treatment rate in the treatment group was significantly higher than that in the control group (P<0.05), and the forced expiratory volume in 1 sec/forced vital capacity (FEV1/FVC), peak expiratory flow (PEF) and 25% peak expiratory flow (PEF25) in the treatment group were significantly higher than those in the control group (P<0.05). The proportions of CD4+CD25+ regulatory T cells in the two groups after drug therapy were significantly increased. The proportion and content per unit volume of peripheral CD4+CD25+ regulatory T cells in the treatment group were obviously higher than those in the control group (P<0.01). After treatment, the levels of interleukin-4 (IL-4), IL-5 and IL-6 in peripheral blood in the two groups were significantly decreased. However, the levels of transferrin-γ (TFN-γ) and IL-10 were significantly increased (P<0.01). The IgE level in the treatment group was also significantly higher than that in the control group (P<0.01). In conclusion, montelukast can regulate the T helper 1 (Th1)/Th2 balance, increase the expression of CD4+CD25+ regulatory T cells, and improve the airway inflammation caused by acute bronchial asthma and the clinical symptoms and lung function of patients with acute bronchial asthma.

Synovial Predictors of Differentiation to Definite Arthritis in Patients With Seronegative Undifferentiated Peripheral Inflammatory Arthritis: microRNA Signature, Histological, and Ultrasound Features.

Objectives: To examine synovial tissue (ST) predictors of clinical differentiation in patients with seronegative undifferentiated peripheral inflammatory arthritis (UPIA).Methods: Fourty-two patients with IgA/IgM-Rheumatoid Factor and anti-citrullinated peptide antibodies negative UPIA, naive to Disease-Modifying Anti-Rheumatic Drugs, underwent Gray Scale (GSUS) and power Doppler (PDUS) evaluation and Ultrasound (US) guided ST biopsy. CD68, CD3, CD21, CD20, and CD31 synovial expression was evaluated by immunohistochemistry. Whole ST microRNA expression was assessed using miScript miRNA PCR Array. Peripheral blood (PB) and synovial fluid (SF) IL-6, VEGF-A, and VEGF-D levels were measured by ELISA and ST TNF expression was assessed by RT-PCR. Each patient was prospectively monitored and classified at baseline and within 1 year as UPIA, Rheumatoid Arthritis (RA), Spondyloarthritis (SpA) or Psoriatic Arthritis (PsA), respectively.Results: At baseline, CD68+ cells were the most common cells within the lining layer (p < 0.001) in seronegative UPIA, directly correlating with GSUS (R = 0.36; p = 0.02) and PDUS (R = 0.55; p < 0.001). Synovial CD31+ vessels count directly correlated with GSUS (R = 0.41; p = 0.01) and PDUS (R = 0.52; p < 0.001). During the follow-up, 6 (14.3%) UPIA reached a definite diagnosis (2 RA, 2 SpA and 2 PsA, respectively). At baseline, UPIA who differentiated had higher GSUS (p = 0.01), PDUS scores (p = 0.02) and higher histological scores for CD68+ (p = 0.005 and p = 0.04 for lining and sublining respectively), sublining CD3+ cells (p = 0.002), CD31+ vessels count (p < 0.001) and higher IL-6 PB levels (p = 0.01) than patients who remained as UPIA. MiRNA PCR Array showed that among the 86 tested miRNA species, at baseline, miR-346 and miR-214 were significantly down-regulated (p = 0.02 for both) in ST of UPIA who differentiated than in patients who remained as UPIA, inversely correlating with the lining CD68+ cells IHC score (R = −0.641; p = 0.048) and CD31+ vessels count (R = −0.665; p = 0.036) and with higher baseline ST expression of TNF (p = 0.014). Finally, logistic regression analysis demonstrated that baseline GSUS and PDUS scores ≥1.5 [OR:22.93 (95%CI:0.98–534.30)] and CD31+ vessels count ≥24.3 [OR:23.66 (95%CI:1.50–373.02)] were independent factors associated with the development of definite arthritis.Conclusions: MiRNA signature, histological and US features of ST may help in the identification of seronegative UPIA with high likelihood of clinical differentiation toward definite seronegative arthritis.

Abstract 3612: Elevated TGFa levels in chronic mylogenous leukemia (CML) patient plasma measured by a highly sensitive single molecule array immunoassay

Abstract Introduction: Recent reports suggest that cytokine and growth factor profiling are prognostic in myelodisplasias and CML. TGF-α and IL-6 plasma levels selectively identified CML patients failing to achieve an early molecular response (EMR), or progressed on imatinib therapy (Nievergall et al, 2016). In patients failing to achieve EMR, the median TGFα concentrations were in the low pg/mL range while IL-6 levels were sub-pg/mL or undetectable. Thus, to accurately and reproducibly measure TGFα and IL-6 levels in blood as prognostic or predictive markers of imatinib response, there is a need for highly sensitive immunoassays. Here we demonstrate the utility of using a digital immunoassay to measure sub-pg/mL levels of TGFα and IL-6 in CML plasma samples assessed for BCR-ABL fusion transcripts. Methods: Single molecule array immunoassays (Simoa) for TGFα and IL-6 were performed on the HD-1 platform (Quanterix), qualified based on precision, reproducibility, linearity, sensitivity according to kit specifications. CML blood samples were obtained from CMBP, LabCorp, Inc, following BCR-ABL e1b2, b2b2, and b3b2 transcript fusion testing by RT-PCR. Results: TGFα and IL-6 concentrations in the plasma of 77 CML patients were determined and compared to levels in healthy controls. TGFα in CML plasma was elevated and ranged ~20-fold (6.13-118.6 pg/mL), in contrast to the low levels and narrow range in healthy controls (range = 1.11-3.17 pg/mL). Median TGFα levels were 10-fold higher in CML patient plasma (median = 18.8 pg/mL) relative to healthy controls (median = 1.8 pg/mL; p &amp;lt;0.0001). IL-6 levels ranged broadly in CML plasma (0.12-12.6 pg/mL) relative to healthy controls (0.3-1.04pg/mL), though median levels were not significantly different (CML = 0.61 vs 0.69, p = 0.873). TGFα and IL-6 concentrations were not significantly correlated. TGFα levels appear elevated in CML samples expressing all 3 BCR-ABL transcripts, however, a larger number of samples enriched in fusion transcripts are being assessed to confirm possible correlations. Conclusions: We have qualified novel highly sensitive single molecule array immunoassays to measure TGFα and IL-6 in the plasma of CML patients and healthy controls, and found significantly elevated levels of TGFα in CML plasma. These results support further investigation of TGFα and IL-6, using sensitive immunoassays, as potential prognostic and predictive markers of CML disease progression and treatment outcome. Citation Format: Ahmed Chenna, Li Cai, Christos Petropoulos, John W. Winslow. Elevated TGFa levels in chronic mylogenous leukemia (CML) patient plasma measured by a highly sensitive single molecule array immunoassay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3612.

Preliminary study of Bim on the early diagnosis and prognosis of the elderly uremia with gastrointestinal nutrition combined with dialysis.

Elderly uremia frequently refers to the end stage of various chronic kidney diseases that threats the patients' health seriously. Enteral nutrition can reduce complications, while the molecular mechanism is still unclear. Mitochondrial protein Bim plays an essential role in regulating inflammation, restraining oxidative stress, and maintaining the balance of the mitochondrial membrane potential and energy production. This study aims to investigate the effect of Bim on the early diagnosis and prognosis of the elderly uremia with gastrointestinal nutrition combined with dialysis. Elderly patients with uremia in our hospital were selected and divided into parenteral nutrition group, enteral nutrition group, and regular treatment group. Healthy volunteers were chosen as the control group. Blood oxygen free radicals were tested by flow cytometry. Blood immune function parameter C-reactive protein and IL-6 levels were determined by Western blot. Bim expression in blood was evaluated by RT-PCR and Western blot. Correlation analysis was performed between Bim level and the prognosis of elderly patients with uremia who received gastrointestinal nutrition therapy. Blood oxygen free radical level was significantly higher in parenteral nutrition group and regular treatment group compared with enteral nutrition group (p< 0.05). C-reactive protein and IL-6 contents were significantly reduced in parenteral nutrition group and regular treatment group compared to those in enteral nutrition group (p< 0.05). The expression of Bim at both mRNA and protein levels was declined in elderly patients with uremia after enteral nutrition combined with dialysis therapy to the normal level. The level of Bim was positively correlated with the severity of elderly uremia. Bim is positively correlated with the severity of elderly uremia, which can be set as a potential specific biomarker, along with reactive oxygen radicals, CRP, IL-6, for the prognosis of elderly uremia.

Jinlida Granules Improve Dysfunction of Hypothalamic-Pituitary-Thyroid Axis in Diabetic Rats Induced by STZ.

Objective We aim to explore the effects and mechanisms of Jinlida granules on the dysfunction of hypothalamic-pituitary-thyroid (HPT) axis in diabetic rats induced by streptozotocin. Methods A total of 48 SD rats were randomized into normal control group (NC, n = 6) and diabetic group (n = 42). Rats in diabetic group were randomly divided into diabetes mellitus (DM) control group, low, medium, and high doses of Jinlida group (JL, JM, and JH), medium dose of Jinlida plus Tongxinluo group (JM + T), metformin group (Met), and Saxagliptin group (Sax) (n = 6 in each group). Diabetic rats were obtained by intraperitoneal injection of streptozotocin and sacrificed at 8 weeks to examine the function of HPT axis. Results Levels of fasting blood glucose (P < 0.05), pIκB, TNFα (P < 0.05), pNF-κB, and IL-6 (P < 0.01) in liver tissue and TSHR mRNA expression (P < 0.01) in diabetic group were significantly increased, while levels of serum T3 and T4, thyroid hormone receptor (TR) mRNA and Dio1 mRNA in liver tissue, and sodium iodide symporter (NIS) mRNA in thyroid tissue in diabetic group were significantly decreased compared with those in NC group (P < 0.01). Among diabetic groups, level of fasting blood glucose in JH, JM + T and Met group was lower (P < 0.05) compared with DM group. However, levels of serum T3 and T4, TR mRNA in liver tissue, TSHR, and NIS mRNA in thyroid tissue in JH, JM + T, Met, and Sax group were significantly increased (P < 0.01) compared to DM group. In contrast, levels of Dio1 mRNA, pI-κB in Met and JM + T groups, pNF-κB in JH, JM + T, and Met group, and TNFα and IL-6 in JM, JH, JM + T, and Met group were significantly decreased (P < 0.05). HE staining showed reduced thyroid follicular epithelium and follicular area, as well as increased colloid area in DM group, indicating impaired synthesis, reabsorption, and secretory of TH in diabetes, which was significantly improved in JH, JM + T, and Met groups. Conclusion HPT axis dysfunction in DM could be significantly improved by Jinlida granules. The mechanism might be associated with the anti-inflammatory effects involving NF-κB pathway. Our findings suggested the potential benefit of Jinlida granules for patients with HPT axis dysfunction and DM, which was to be verified by more experimental and clinical studies.

Evidence for interplay among antibacterial-induced gut microbiota disturbance, neuro-inflammation, and anxiety in mice.

The aim of the present study was to determine whether there is the mechanistic connection between antibacterial-dependent gut microbiota disturbance and anxiety. First, exposure of mice to ampicillin caused anxiety and colitis and increased the population of Proteobacteria, particularly Klebsiella oxytoca, in gut microbiota and fecal and blood lipopolysaccharide levels, while decreasing lactobacilli population including Lactobacillus reuteri. Next, treatments with fecal microbiota of ampicillin-treated mouse (FAP), K. oxytoca, or lipopolysaccharide isolated from K. oxytoca (KL) induced anxiety and colitis in mice and increased blood corticosterone, IL-6, and lipopolysaccharide levels. Moreover, these treatments also increased the recruitment of microglia (Iba1+), monocytes (CD11b+/CD45+), and dendritic cells (CD11b+/CD11c+) to the hippocampus, as well as the population of apoptotic neuron cells (caspase-3+/NeuN+) in the brain. Furthermore, ampicillin, K. oxytoca, and KL induced NF-κB activation and IL-1β and TNF-α expression in the colon and brain as well as increased gut membrane permeability. Finally, oral administration of L. reuteri alleviated ampicillin-induced anxiety and colitis. These results suggest that ampicillin exposure can cause anxiety through neuro-inflammation which can be induced by monocyte/macrophage-activated gastrointestinal inflammation and elevated Proteobacteria population including K. oxytoca, while treatment with lactobacilli suppresses it.

Abstract P-269: BLOOD PURIFICATION TREATMENT FOR SEVERE CYTOKINE RELEASE SYNDROME AFTER CHIMERIC ANTIGEN RECEPTOR T CELL THERAPY: CASE REPORT AND LITERATURE REVIEW.

Aims & Objectives: To evaluate the effectiveness of Blood Purification treatment for Severe Cytokine Release Syndrome after Chimeric Antigen Receptor T cell Therapy in pediatrics relapsed acute lymphoblastic leukemia. Methods We reported a case of 11 years old boy with relapsed ALL developed the severe CRS rapidly after treated with CAR-T therapy and reviewed the literature. Results The boy developed to severe cytokine-release syndrome rapidly after treated with CAR-T cellular therapy within 3 days. The CRS was characterized as high fever, hypotension, capillary leakage, edema and high IL-6 level in blood (20587pg/ml). After the failure of the anti-IL-6 antibody treatment, this patient was treated with blood purification combined with plasma exchange and CVVHDF in emergency, and the CRS was ultimately controlled. This paper reported the treatment process of rapid introduction of blood purification therapy for severe CRS in PICU, By searching the literature, we found that severe CRS patients required intensive care with respiratory support (nasal cannula or mechanical ventilation) and vasopressor support. Serum IL-6 levels was positive collected with the severity of CRS after CAR-T-cell Therapy. Anti-IL-6 antibody therapy has been recommended for severe CRS, but seldom literature reported blood purification used in severe CRS. Conclusions Blood purification has advantage of eliminated inflammatory cytokines for the treatment of CRS after CAR-T.We provided a promising alternative to treating severe CRS after the failure of conventional therapy such as anti-IL-6 antibody treatment in CAR-T therapy patients.

Expression Levels of Interferon Regulatory Factor 5 (IRF5) and Related Inflammatory Cytokines Associated with Severity, Prognosis, and Causative Pathogen in Patients with Community-Acquired Pneumonia.

BackgroundCommunity-acquired pneumonia (CAP) is a common disease with significant morbidity and mortality. Interferon regulatory factor 5 (IRF5), which induces type I interferons (IFNs) and cytokines such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, and interferon gamma-induced protein (IP)10, is a key transcription factor involved in controlling the expression of proinflammatory cytokines and responses to infection. Here, we carefully investigated the role of IRF5 in regulating immune responses to CAP.Material/MethodsQRT-PCR was used to detect the mRNA levels of IRF5, IL-6, IL-10, IP10, TNF-α, and IFN-α in the peripheral blood of 71 CAP patients and 31 healthy controls, as well as in the bronchoalveolar lavage cells of 20 patients with CAP and 23 patients with lung cancer (using samples from the unaffected lung). Flow cytometry was performed to detect the protein level of IRF5, and a CBA flex set was used to detect the levels of these cytokines in the volunteers.ResultsThe expression levels of IRF5 and its related cytokines were significantly increased in CAP patients compared with the controls. Additionally, IRF5, IL-6, IL-10, and IP10 levels were found to be related with the severity of CAP. Furthermore, the levels of IRF5 and IFN-α increased significantly in the early phase of pneumonia caused by influenza virus infection.ConclusionsIRF5 and its related inflammatory cytokines are associated with the severity, prognosis, and causative pathogen of CAP patients. This finding may provide new drug targets for the prevention and treatment of severe pneumonia caused by influenza virus.

Lysophosphatidylcholine as a predictor of postoperative complications after colorectal cancer surgery.

Lysophosphatidylcholine (LPC), which is generated from phosphatidylcholine (PC) and metabolized by autotaxin (ATX), modulates immune responses via its anti-inflammatory property. We investigated the association between LPC and postoperative complications (POCs) after colorectal cancer surgery (CRC). The subjects of this study were 43 patients who underwent surgery for CRC. Peripheral blood samples were collected preoperatively and immediately after surgery, and on postoperative days (PODs) 1, 3, 5, and 7. Patients were divided into a No-POC group (n = 33) and a POC group (n = 10). Blood LPC, IL-6, PC, and ATX levels were measured by specific enzymatic assays or ELISA. The postoperative to preoperative LPC ratios were lowest on POD 1 in both groups. The POC group had significantly lower LPC ratios throughout the perioperative period than the No-POC group. The LPC ratios were inversely correlated with IL-6. The predictive impact of LPC ratios on POCs was demonstrated by ROC analysis (cut-off 51.2%, AUC 0.798) and multivariate analysis (OR 15.1, P = 0.01). The postoperative PC ratios decreased more after surgery in the POC group. ATX levels did not change significantly in either group. Decreased postoperative LPC is associated with increased postoperative inflammatory response and POCs. The decreased PC supply to the circulation is a mechanism of the postoperative LPC decrease.

Extracorporeal Detoxification in Abdominal Sepsis in Cancer Patients

The purpose is to evaluate the detoxification effects of the polymyxin sorption columns and filtration detoxification using polymethyl methacrylate membranes in abdominal sepsis in cancer patients. Materials and Methods . We examined 226 patients with oncological diseases of abdominal organs complicated by abdominal sepsis postsurgery. In 50 cases, septic shock was reported. In 173 patients an acute renal injury (ARI) was diagnosed in the structure of organ failures, of which a combination with acute respiratory distress syndrome (ARDS) was diagnosed in 61 patients. The severity was 26.3±3.3 points (APACHE-II scale), 10.2±2.5 points (SOFA scale), and 4.3±1.8 points (qSOFA scale). Microbiological identification was obtained in 155 (68.6%) cases. The polymyxin column sorption was used in 86 patients 2–6 hours after sepsis was diagnosed with the EAA greater than 0.5. The blood flow rate was 80–150 mL/min; the duration was 120–240 min; the sorption frequency was 2–3 sessions at a 24-hour interval. If ARI and ARDS were developed, detoxification by filtration using a dialyzer with a BK-1.6F polymethylmethacrylate membrane was included in the complex treatment of 144 patients. The detoxification was carried out for 8–12 hours changing the dialyzer every 4 hours. Results . A statistically significant decreases of hyperthermia, leukocytosis, neutrophilia, procalcitonin, and the EAA test values were revealed after the completion of the sorption treatment. Normalization of hemodynamic parameters, increase of the oxygenation index, and SOFA scoring decrease by 5.6±2.1 points (P<0.05) were found. PCT and IL-6 blood levels decreased from 6.7±2.7 ng/mL to 2.3±0.6 ng/mL and from 7300±7700 pg/mL to 860±180 pg/mL, respectively, as determined 60 minutes after completion of filtration detoxification procedure (P<0.05). The SOFA index decreased by 4.1±1.1 points (P<0.05). Conclusion . The use of polymyxin column sorption and filtration detoxification using a polymethyl metacrylate membrane improves the results of treatment of abdominal sepsis in cancer patients.

Effect of Aerobic Exercise on Treg and Th17 of Rats with Ischemic Cardiomyopathy.

Immune activation and inflammation participate in the progression of chronic heart failure (CHF). Th17 cells and CD4+CD25+ regulatory T (Treg) cells both come from naive Th cells and share reciprocal development pathways but exhibit opposite effects. We hypothesized that the Th17/Treg balance was impaired in patients with CHF, and exercise can improve it. Rats with ischemic cardiomyopathy were prepared by ligaturing the left anterior descending branch of the left coronary artery. Rats in training group were trained with treadmill; Th17 cells increased significantly while Treg cells significantly decreased in s by flow cytometry, and the peripheral blood level of IL-6, IL-17, and TNF-α was obviously elevated by ELISA assay. We found that Th17/Treg balance is impaired in CHF rats, suggesting Th17/Treg imbalance potentially plays a role in the pathogenesis of CHF. Exercise can improve Th17/Treg imbalance, which also improves cardiac function of CHF.

Effects of double-dose antihistamine or combined therapy in allergic rhinitis

Objective:To compare the efficacy and side effects of combined therapy with single-dose oral antihistamine and intranasal corticosteroid to monotherapy with double-dose oral antihistamine in the treatment of seasonal allergic rhinitis. Method:Eighty-two patients with seasonal allergic rhinitis caused by cypress pollen were enrolled in a randomized, parallel-group studycomparing 2 weeks therapy of either 10mg oral ebastine plus 200 μg intranasal mometasone furoate once daily (combined group) or 20 mg oral ebastine once daily (double-dose group) during the pollen season. Daily rhinoconjunctivitis symptom score and rescue medication use were recorded in both groups. After the treatment period, questionnaires were used to survey the side effects of medicines and dosage form preference of the patients. The levels of IL-6, IL-8 and TNF-α in the peripheral blood were measured before and after the therapy. Result:During the cypress pollen season, the daily rhinoconjunctivitis symptom score of the combined group (n=42, 3.7±0.4) was significantly lower than that of double-dose group (n=40, 4.5±0.5), P<0.001. The daily rescue medication score of the combined group (1.3±0.6) was also significantly lower than double-dose group(1.7±0.7), P<0.001. The daily medication cost of combined group was 7.08±0.33 Yuan, which was less than that of double-dose group (7.28±0.51 Yuan, P=0.002). There was no statistical difference in the rate of adverse reactions between the two groups. The peripheral levels of IL-6, IL-8 and TNF-α in two groups did not show significant difference at the end of therapy . Conclusion:The combined therapy with single-dose oral antihistamine and intranasal corticosteroid was superior to the monotherapy with double-dose oral antihistamine in the treatment of seasonal allergic rhinitis in our study.

Evaluation of the Curative Effect of Umbilical Cord Mesenchymal Stem Cell Therapy for Knee Arthritis in Dogs Using Imaging Technology.

Objective The aim of this study was to assess the efficacy of canine umbilical cord mesenchymal stem cells (UC-MSCs) on the treatment of knee osteoarthritis in dogs. Methods Eight dogs were evenly assigned to two groups. The canine model of knee osteoarthritis was established by surgical manipulation of knee articular cartilage on these eight dogs. UC-MSCs were isolated from umbilical cord Wharton's jelly by 0.1% type collagenase I and identified by immunofluorescence staining and adipogenic and osteogenic differentiation in vitro. A suspension of allogeneic UC-MSCs (1 × 106) and an equal amount of physiological saline was injected into the cavitas articularis in the treated and untreated control groups, respectively, on days 1 and 3 posttreatment. The structure of the canine knee joint was observed by magnetic resonance imaging (MRI), B-mode ultrasonography, and X-ray imaging at the 3rd, 7th, 14th, and 28th days after treatment. Concurrently, the levels of IL-6, IL-7, and TNF-α in the blood of the examined dogs were measured. Moreover, the recovery of cartilage and patella surface in the treated group and untreated group was compared using a scanning electron microscope (SEM) after a 35-day treatment. Results Results revealed that the isolated cells were UC-MSCs, because they were positive for CD44 and negative for CD34 surface markers, and the cells were differentiated into adipocytes and osteoblasts. Imaging technology showed that as treatment time increased, the high signal in the MRI T2-weighted images decreased, the echo-free space in B ultrasonography images disappeared basically, and the continuous linear hypoechoic region at the trochlear sulcus thickened. On X-ray images, the serrate defect at the ventral cortex of the patella improved, and the low-density gap of the ventral patella and trochlear crest gradually increased in the treated group. On the contrary, the high signal in the MRI T2-weighted images and the echo-free space in B ultrasonography images still increased after a 14-day treatment in the untreated control group, and the linear hypoechoic region was discontinuous. On the X-ray images, there was no improvement in the serrate defect of the ventral cortex of the patella. Results for inflammatory factors showed that the blood levels of IL-6, IL-7, and TNF-α of the untreated control group were significantly higher than those of the treated group (P < 0.05) 7–14 days posttreatment. The result of SEM showed that the cartilage neogenesis in the treated group had visible neonatal tissue and more irregular arrangement of new tissue fibers than that of the untreated control group. Furthermore, more vacuoles but without collagen fibers were observed in the cartilage of the untreated control group, and the thickness of the neogenetic cartilage in the treated group (65.13 ± 5.29, 65.30 ± 5.83) and the untreated control group (34.27 ± 5.42) showed a significant difference (P < 0.01). Conclusion Significantly higher improvement in cartilage neogenesis and recovery was observed in the treated group compared to the untreated control group. The joint fluid and the inflammatory response in the treated group decreased. Moreover, improved recovery in the neogenetic cartilage, damaged skin fascia, and muscle tissue around the joints was more significant in the treated group than in the untreated control group. In conclusion, canine UC-MSCs promote the repair of cartilage and patella injury in osteoarthritis, improve the healing of the surrounding tissues, and reduce the inflammatory response.

Metabolic and IL-6-Induced Inflammatory Responses in High-Intensity Intermittent Exercise among Type 2 Diabetes Patients with Sarcopenia

Objective: The aim of this study was to examine the effects of high-intensity intermittent exercise (HIIE) on features of immunometabolism by comparing elderly female sarcopenia and non-sarcopenia in elderly female patients with type 2 diabetes (T2MD). Differences in metabolism and inflammatory responses between the two groups were compared. Methods: 6 elderly female sarcopenia patients with T2MD served as sarcopenia group, and 7 elderly female non-sarcopenia patients with T2MD served as control subjects. Using dual energy X-ray absorptiometry (DXA) to the subjects’ body fat compositions was measured. All subjects underwent three high-intensity Wingate tests at 5-minute intervals, and peak and average power during each Wingate trial were recorded. Blood samples were collected immediately after the test was completed. Peripheral blood levels of the inflammatory cytokine IL-6, which is related to mitosis, were measured in both groups before and after HIIE by ELISA. Results: The non-sarcopenia group had a higher metabolic rate than the sarcopenia group. Sarcopenia had no significant effect on the differences in the IL-6 inflammatory response (p = 0.430). Conclusion: The metabolic energy and rate during HIIE differed between the two groups. Non-sarcopenia group exhibited higher metabolic levels. No significant difference between groups was observed in the IL-6 inflammatory response during HIIE.