Blood Levels Of IL-6 Research Articles

How to Monitor the Neuroimmune Biological Response in Patients Affected by Immune Alteration-Related Systemic Diseases.

The clinical management of patients affected by systemic diseases, including cancer and autoimmune diseases, is generally founded on the evaluation of the only markers related to the single disease rather than the biological immuno-inflammatory response of patients, despite the fundamental role of cytokine network in the pathogenesis of cancer and autoimmunity is well known. Cancer progression has appeared to be associated with a progressive decline in the blood levels of the main antitumor cytokines, including IL-2 and IL-12, in association with an increase in those of inflammatory cytokines, including IL-6, TNF-alpha, and IL-1-beta, and immunosuppressive cytokines, namely TGF-beta and IL-10. On the other hand, the severity of the autoimmune diseases has been proven to be greater in the presence of high blood levels of IL-17, TNF-alpha, IL-6, IL-1-beta, IFN-gamma, and IL-18, in association with low levels of TGF-beta and IL-10. However, because of excessive cost and complexity of analyzing the data regarding the secretion of the single cytokines, the relation between lymphocyte-induced immune activation and monocyte-macrophage-mediated immunosuppression has been recently proven to be expressed by the simple lymphocyte-to-monocyte ratio (LMR). The evidence of low LMR values has appeared to correlate with a poor prognosis in cancer and with a disease control in the autoimmune diseases. Moreover, since the in vivo immunoinflammatory response is physiologically under a neuroendocrine modulation, for the evaluation of patient biological response it would be necessary to investigate the function of at least the two main neuroendocrine structures involved in the neuroendocrine modulation of the immune responses, consisting of the hypothalamic-pituitary-adrenal axis and the pineal gland, since the lack of physiological circadian rhythm of cortisol and pineal hormone melatonin has appeared to be associated with a worse prognosis in the human systemic diseases.

The Influence of Hyperlipidemia on Endothelial Function of FPN1 Tek-Cre Mice and the Intervention Effect of Tetramethylpyrazine

Background/Aims: Systemic iron homeostasis is strictly governed in mammals; however, disordered iron metabolism (such as excess iron burden) is recognized as a risk factor for various types of diseases including AS (Atherosclerosis). The hepcidin-ferroportin axis plays the key role in regulation of iron homeostasis and modulation of this signaling could be a potential therapeutic strategy in the treatment of these diseases. TMP (Tetramethylpyrazine) has been reported to have therapeutical effect on AS. Here, we aimed to investigate the effect of iron overload under hyperlipidemia condition on the endothelial injury, inflammation and oxidative stress by employing FPN1 Tek-cre mouse model with or without TMP intervention. Methods: Subjects for this study were 80 FPN1 Tek-cre mice and 40 C57BL/6 mice and we randomly divided them into six groups: Group N: C57BL/6 mice with normal diet, Group M: C57BL/6 mice with high-fat diet, Group FN: FPN1 Tek-cre mice with normal diet, Group FNT: FPN1 Tek-cre mice with normal diet and TMP injection, Group FM: FPN1 Tek-cre mice with high-fat diet, Group FMT: FPN1 Tek-cre mice with high-fat diet and TMP injection. After seven days of treatment, blood samples were obtained to detect the levels of blood lipids, Hepcidin, NO, ET-1, ROS, MDA, SOD, IL-1, IL-6 and TNF-α respectively. The liver and aorta were used for testing the lipid deposition by using hematoxylin and eosin(HE). Results: Hyperlipidemia could cause iron overload in the aorta and increased serum hepcidin level, particularly in FPN1 Tek-cre mice, and can be reversed by TMP intervention. Knockout of Fpn1 induced increase of serum hepcidin, exacerbated endothelial dysfunction, oxidative stress and inflammatory response, particularly under hyperlipidemia condition. TMP intervention attenuated these processes. Conclusions: Our study signifies the potential application of certain natural compounds to ameliorating iron disorders induced by hyperlipidemia and protecting on endothelial function through modulation of hepcidin-ferroportin signaling.

Experimental Study of Phlebitis Ointment Administration in Acute Superficial Thrombophlebitis.

Acute superficial thrombophlebitis is a venous system disease. Animal models with mannitol induced phlebitis were treated with an orally administered “phlebitis ointment.” 24 rabbits were randomly divided into 4 groups. The therapy group was treated with “phlebitis ointment” and a control group received “Mai Luo Shu Tong granules.” Levels of blood TNF-α, IL-6, CRP, and IL-1β were measured. The tissue expression levels of NF-КBp65 and PKC genes were evaluated. The therapy group showed a better improvement of the clinical status and similar vascular morphology than the control group. A blank group showed no vascular changes through pathological investigation. In contrast, significant vascular changes were seen in the model group. The control group showed slight vascular modifications. Small thrombi could be found in the lumen despite the intact tunica intima. Both control and therapy group showed less inflammatory cells infiltration than the model group and upregulation of NF-КBp65 and PKC genes. The phlebitis ointment reduced the levels of necrosis factor-α, interleukin-6, C-reactive protein, and interleukin-1ß. The expressions of NF-КBp65 and PKC genes, which are the primary mechanisms underlying the development of thrombophlebitis, were improved significantly in tissues of both therapy group and control group.

The Effects of Coenzyme Q10 on Inflammation Markers in Streptozotocin-Induced Diabetic Rats

Background: Coenzyme Q10 is a well-known cofactor in the mitochondrial electron transport chain required for ATP production. Coenzyme Q10 is recognized as an intracellular antioxidant that protects cell membrane phospholipids, mitochondrial membrane protein, and plasma low-density lipoprotein against oxidative damage caused by free radicals. Diabetes and its complications have been related to increased levels of free radicals and systemic proinflammatory cytokines and to an abnormal lipid profile. The aim of this study was to investigate the effects of coenzyme Q10 supplementation on some cytokine levels in streptozotocin-induced diabetic rats.Materials, Methods & Results: In this study, 38 healthy, adult male rats were used. The rats were divided into 5 groups. All animals were housed in separated cages during the four weeks. The animals in group 1 was fed standard rat pellets for 4 weeks. It was administered at 0.3 mL corn oil intraperitoneally daily for four weeks in group 2 animals. The animals in group 3 was injected intraperitoneally with 10 mg/kg CoQ10 daily for 4 weeks. Group 4 was made diabetic by subcutaneous injections of streptozotocin at dose of 40 mg/kg in 0.1 M citrate buffer (pH 4.5) single daily dose for two days and group 5 was made diabetic by subcutaneous injections of streptozotocin at dose of 40 mg/kg in 0.1 M citrate buffer (pH 4.5) single daily dose for two days and then was injected intraperitoneally with 10 mg/kg CoQ10 daily for 4 weeks. During the experiment, three animals from group 4 and one animals from group 5 were died due to streptozotocin-induced hypoglycemia. At the end of the study, blood samples were taken from all animals. In these blood samples, IL-4, IL-6, IL-10 and TNF-α plasma levels were determined with ELISA using sandwich enzyme-linked immunosorbent method via commercial kits. In this study, IL-4 level as an anti-inflammatory cytokine significantly decreased (P < 0.05) with diabetes induction compared to control group level. IL-10 level in diabetic group was statistically different (P < 0.05) from control group level. CoQ10 application to diabetic animals improved the falling in IL-10 level of diabetic group (P < 0.05). IL-6 and TNF-α levels in diabetic group significantly increased (P < 0.05) in parallel with each other compared to control group levels. The same parameters were reduced (P < 0.05) by CoQ10 application in diabetic animals.Discussion: In this study, the occurred changes in pro- and anti-inflammatory cytokines with experimentally induced diabetes are expected results and these results are consistent with some studies related diabetes. These results may be considered to hazardous effects and inflammation caused by diabetes on liver, pancreas and other tissues. CoQ10 suppressed the increments in plasma pro-inflammatory cytokine levels, whereas it restored the reducing in anti-inflammatory cytokine levels arising due to diabetes. The obtained results from this study after CoQ10 application supported similar studies used CoQ10 application against deleterious effects of diabetes in animals and humans. Therefore, it is possible to say that CoQ10 may play important role in regulation of imbalance between inflammation markers in diabetes conditions and further studies are needed to clear the beneficial effects of CoQ10 treatment on the other inflammation markers in diabetes status.

Characteristic Comparison of Meningitis and Non-meningitis of Streptococcus suis in an Experimentally Infected Porcine Model.

This study tested the differences of meningitis and non-meningitis of Streptococcus suis (SS). In this study, an infected pig model of streptococcal meningitis was established. Compared with the non-meningitis Streptococcus suis group (JZLQ001 group), the meningitis Streptococcus suis group (JZLQ022) exhibited neurological symptoms, such as ataxia and foaming at the mouth, and the brain showed a large area of congestion at 5days post-infection (p.i.). Moreover, bacterial counts, white blood cells (WBCs), neutrophils, and blood glucose in the blood reached a peak and were significantly higher than those of the JZLQ001 group at 3days p.i. These values then decreased at 5days p.i. However, the content of total protein in the blood was lower in the JZLQ022 group than that in the JZLQ001 group, and the difference was most significant at 5days p.i. When neurological symptoms appeared on 5days p.i., the bacterial counts in the brain in the JZLQ022 group were significantly higher than those in the JZLQ001 group. The levels of cytokines in the peripheral blood and cerebrospinal fluid (CSF) were an important indicator of inflammation. By ELISA detection, the secretion levels of IL-6, IL-8, and IL-17 in the peripheral blood in the JZLQ022 group were significantly higher than those in the JZLQ001 group at 12 and 24h and 3days p.i.; however, TNF-α showed no difference. At 5days p.i., the secretion levels of IL-6, IL-8, and IL-17 in the JZLQ022 group were significantly lower than those in the JZLQ001 group. The results were similar in CSF. HE staining revealed that the JZLQ022 group exhibited neuronophagia and hyperemia in the brain, but no change was found in the JZLQ001 group. A further study investigating the impact of meningitis Streptococcus suis on blood-brain barrier (BBB) integrity found that the brain tissue content of endogenous IgG in the JZLQ022 group was significantly higher than that in the JZLQ001 group. The present study demonstrated that pigs infected with meningitis and non-meningitis Streptococcus suis exhibit significant differences in immunological aspects such as bacterial counts, WBCs, neutrophils, blood glucose and total protein in the peripheral blood, the secretion levels of IL-6, IL-8, and IL-17, and BBB integrity. These data provide the necessary evidence to better understand SS meningitis.

Value of serum inflammatory factors in differential diagnosis of systemic juvenile idiopathic arthritis and sepsis in children

Objective To evaluate the value of soluble interleukin 2 receptor (sIL-2R), interleukin (IL)-6, IL-10 and tumor necrosis factor-α (TNF-α) used in differential diagnosis of systemic juvenile idiopathic arthritis (sJIA) and sepsis in children. Methods Each of 41 children with sJIA and sepsis were enrolled and 41 healthy children were selected as the healthy control group at Children′s Hospital of Nanjing Medical University from January 2015 to July 2017.Levels of serum sIL-2R, IL-6, IL-10, TNF-α and peripheral blood levels of white blood cells (WBC), hemoglobin (Hb), platelets (PLT), high sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR) and procalcitonin (PCT) were compared between the sJIA group and sepsis group before treatment and those of the healthy control group. Results Peripheral blood levels of WBC, Hb, PLT, CRP, ESR and PCT in the healthy control group were (8.43±2.35)×109/L, (124.46±8.76) g/L, (298.45±100.23)×109/L, (11.32±5.76) mg/L, (18.32±9.33) mm/1 h, (0.27±0.17) μg/L and the levels of serum sIL-2R, IL-6, IL-10, TNF-α were (483.24±255.33) kU/L, (7.38±4.02) ng/L, (5.45±3.06) ng/L, (8.23±3.03) ng/L, respectively.Peripheral blood levels of WBC, Hb, PLT, CRP, ESR and PCT in the sJIA group before treatment were (17.53±7.98)×109/L, (105.76±13.33) g/L, (389.43±176.34)×109/L, (88.32±43.21) mg/L, (55.32±34.23) mm/1 h, (0.53±0.24) μg/L and the levels of serum sIL-2R, IL-6, IL-10, TNF-α were (945.35±436.75) kU/L, (132.39±58.43) ng/L, (7.02±5.12) ng/L, (14.32±7.95) ng/L.Peripheral blood levels of WBC, Hb, PLT, CRP, ESR and PCT in sepsis group before treatment were (16.88±6.54)×109/L, (102.95±20.18) g/L, (302.87±124.45)×109/L, (60.41±33.24) mg/L, (53.75±28.43) mm/1 h, (2.84±1.76) μg/L and the levels of serum sIL-2R, IL-6, IL-10, TNF-α were (2 476.36±1 574.11) kU/L, (39.47±20.32) ng/L, (6.31±4.04) ng/L, (15.87±6.32) ng/L.Blood levels of WBC, CRP, ESR, PCT, sIL-2R, IL-6 and TNF-α in the sJIA and the sepsis group were significantly higher than those in healthy control group.Serum levels of sIL-2R and PCT in the sJIA group were obviously lower than those in the sepsis group, but the level of IL-6 was higher than that in the sepsis group. Conclusion Combined detection of blood sIL-2R, IL-6 and PCT can provide a reference and reduce mistaken diagnosis of sJIA and sepsis in the earlier clinical stage. Key words: Soluble interleukin 2 receptor; Interleukin-6; Interleukin-10; Tumor necrosis factor-α; Systemic juvenile idiopathic arthritis; Sepsis

Крипторхізм та варикоцеле: ще один погляд на причини старту аутоагресії

Objective. To determine the role of oxidative stress and inflammation in the pathogenesis of subfertility/infertility and formation of autoimmunity in patients with cryptorchidism and varicocele. Material and metods. Blood levels of MDA and IL-6 were measured in 48 boys with cryptorchidism and 20 healthy subjects. The spermal parameters (motility, morphology), blood levels of MDA and IL-6 were measured in 22 men with varicocele and 21 healthy subjects. The statistical processing was performed with using noparametrical methods and standart computer programs (Statistica Version 6, StatSoft, Inc.; SPSS Statistics 17.0, IBM). Results. We showed that the level of МDA was significantly higher in blood of the cryptorchidism group compared with the control group (p=0.003). The blood serum concentration of IL-6 in the group with bilateral cryptorchidism as compared to the group with unilateral cryptorchidism was higher (p=0.001). We revealed that the levels of MDA, IL-6 and seminal parameters (low motility, sperm abnormalities) was higher in patients with varicocele compared to the control group (p<0.05; p=0.011). In our opinion, MDA is the most reliable and decisive biochemical marker displaying oxidative damage in undescended testes and varicocele, and may be triggered by an autoimmune response. Conclusions. The level of МDA is higher in blood of groups with bilateral and unilateral cryptorchidism, as well as in blood and seminal plasma of patients with varicocele. The higher level of MDA correlates with low motility and higher level of sperm abnormalities in patients with varicocele. The tendency of increased IL-6 level in blood of groups with bilateral and unilateral cryptorchidism, also in blood and seminal plasma of patients with varicocele is a ponderable factor of oxidative stress and a trigger of automunity.

Evaluation of Curcumin's effect on inflammation in hemodialysis patients

Despite advances in prevention of inflammatory milieu with different anti-inflammatory modalities in hemodialysis patients the rate of inflammatory markers in this population are still high. Inflammation is considered as a major player in uremia associated with morbidity and mortality in hemodialysis patients. The aim of this study was to evaluate the turmeric s effects on reduction of inflammatory markers in hemodialysis patients. Hemodialysis patients over 18 years were recruited after fulfilling the inclusion criteria. Seventy-one hemodialysis patients were randomized into two groups: the trial group (n=35) and the controls (n=36); a randomization numeric table was used for allocation sequence. Trial group received turmeric and control group received placebo for 12 weeks. Biochemical determinations included levels of serum albumin (Alb), potassium (K), blood urea nitrogen (BUN), serum creatinine (Cr), IL-6 level, TNF-α, and liver function tests and hs-CRP at the start and end of the study were measured. Although there was a significant reduction in hs-CRP level, IL-6 level and TNF-α level in turmeric group (p=0.002, p=0.001, p=0.001), there was no statistical difference between intervention and control groups. Albumin level was significantly increased in turmeric group (p=0.001) and no meaningful changes were seen in potassium or liver function tests neither within nor between groups. Programmed ingestion of turmeric has no adverse effects and reduces plasma level of hs-CRP, IL-6 and TNF-α accompanying with increases albumin levels in hemodialysis patients. Turmeric can be considered as an effective anti-inflammatory supplement in hemodialysis patients.

Anxiolytic-like effect of Bifidobacterium adolescentis IM38 in mice with or without immobilisation stress.

To better understand the role of gut microbiota in the anxiety, we isolated bifidobacteria and lactobacilli from the human faecal microbiota, investigated their inhibitory effects on the expression of interleukin (IL)-6 and tumour necrosis factor (TNF)-α in lipopolysaccharide-stimulated macrophages, and examined the anxiolytic-like effect of Bifidobacterium adolescentis IM38 in mice treated with or without immobilisation stress using the elevated plus maze (EPM) task. Oral administration of IM38 at a dose of 1×109 cfu/mouse showed a significant anxiolytic-like effect both in mice exposed to immobilisation stress and in control mice using the EPM test (P<0.05). Moreover, IM38 treatment significantly increased the amount of time spent on open arms and open arm entries. The anxiolytic-like effect of IM38 was comparable to that of buspirone (1 mg/kg). Moreover, this anxiolytic-like effect was blocked by treatment with flumazenil (3 mg/kg, i.p.), a benzodiazepine receptor antagonist, but was not affected by treatment with bicuculine or WAY-100635. IM38 treatment also reduced the blood levels of corticosterone and IL-6 in mice with or without immobilisation stress, whereas this effect was abolished by treatment with flumazenil. IM38 treatment also reduced the blood TNF-α level in mice subjected to immobilisation stress but not in normal control mice. Treatment with flumazenil also significantly increased TNF-α and IL-6 levels in immobilisation stress-free mice treated with IM38. These findings suggest that IM38 may attenuate anxiety through modulation of the benzodiazepine site on the GABAA receptor and modulate stress-related cytokine expression.

Role of β2-Adrenoreceptors in Adrenergic Anti-Inflammatory Mechanism in Sepsis.

Experiments on random-bred albino mice showed that of β2-adrenoreceptor agonist hexaprenaline sulfate significantly reduced mortality of mice from experimental sepsis (intraperitoneal administration of E. coli) in 4 and 24 h after modeling by reducing blood levels of proinflammatory cytokines TNFα, IL-1β, and IL-6. The antagonist of β2AR ICI-118,551 eliminated this effect.

P.1.h.028 - Knockdown of Bcl-xL in the rat hippocampus increased immobility in the forced swim test

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.

Clinical effect of mesalazine combined with bifidobacterium in the treatment of ulcerative colitis and its effect on serum inflammatory cytokines

Objective To observe the clinical effect of mesalazine combined with bifidobacterium in the treatment of ulcerative colitis and its effect on serum inflammatory cytokines. Methods 80 patients with ulcerative colitis were selected as the subjects.Auording to the digital table, the patients were randomly divided into observation group(40 cases) and control group(40 cases) by random number tables.The control group was treated with oral mesalazine only.The observation group was treated with bifidobacterium on the basis of the control group.Both two groups were treated for 8 weeks.Before and after treatment, the symptoms and microscopic manifestations were observed.The levels of CRP, TNF-α, IL-6 and IL-8 in venous blood were measured before and after treatment in the morning, and the clinical curative effect was evaluated. Results The proportions of diarrhea, abdominal pain and mucus bloody in the control group and the observation group were 20.0% and 0.0%, 22.5% and 2.5%, 20.0% and 0.0%, respectively, which were significantly lower than those before treatment(χ2=46.036, 72.381, 26.467, 52.379, 22.175, 48.000, all P<0.01). The improvement of diarrhea, abdominal pain and mucus bloody of the observation group was better than those of the control group(χ2=8.941, 7.895, 9.574, all P<0.05). The percentages of ulcers, erosions and bleeding points in the observation group and the control group were 22.5% and 5.0%, 32.5% and 10.0%, 37.5% and 7.5%, respectively, which were significantly lower than those before treatment(χ2=31.427, 48.813, 12.832, 32.273, 29.574, 64.962, all P<0.01). The improvement of ulcer, erosive and bleeding in the observation group was better than those in the control group(χ2=5.084, 6.74, 10.853, all P<0.05). The levels of CRP, TNF-α, IL-6 and IL-8 in the control group and observation group were (13.6±3.6)mg/L and (7.8±1.2)mg/L, (28.4±9.6)ng/L and (15.6±7.1)ng/L, (141.3±21.4)ng/L and (90.5±14.7)ng/L, (202.4±32.8)ng/L and (155.2±25.4)ng/L, respectively, which were significantly lower than those before treatment (t=15.525 and 20.672, 13.851 and 17.524, 8.243 and 12.021, 9.101 and 11.132, all P<0.01), the CRP, TNF-α, IL-6 and IL-8 levels in the observation group were significantly lower than those in the control group(t=7.456, 6.325, 7.543, all P<0.01). The effective rate in the observation group was 97.5%(39/40), which was significantly higher than that in the control group (77.5%, 31/40), the difference was statistically significant(χ2=7.680, P<0.05). Conclusion Mesalazine combined with bifidobacterium has exact clinical effect in the treatment of ulcerative colitis, it is more effective in improving clinical symptoms and microscopic manifestations, and can reduce the level of serum proinflammatory cytokines.It is worthy to be used. Key words: Colitis, ulcerative; Melazine; Bifidobacterium virescens; Inflammatory factors

A double blind randomized experimental study on the use of IgM-enriched polyclonal immunoglobulins in an animal model of pneumonia developing shock

BackgroundPatients with severe pneumonia often develop septic shock. IgM-enriched immunoglobulins have been proposed as a potential adjuvant therapy for septic shock. While in vitro data are available on the possible mechanisms of action of IgM-enriched immunoglobulins, the results of the in vivo experimental studies are non-univocal and, overall, unconvincing. We designed this double blinded randomized controlled study to test whether IgM-enriched immunoglobulins administered as rescue treatment in a pneumonia model developing shock, could either limit lung damage and/or contain systemic inflammatory response. MethodsThirty-eight Sprague Dawley rats were ventilated with injurious ventilation for 30min to prime the lung. The rats were subsequently randomized to received intratracheal instillation of either lipopolysaccharide (LPS) (12mg/kg) or placebo followed by 3.5h of protective mechanical ventilation. IgM-enriched immunoglobulins at 25mg/h (0.5mL/h) or saline were intravenously administered in the last hour of mechanical ventilation. During the experiment, gas exchange and hemodynamic measurements were recorded. Thereafter, the animals were sacrificed, and blood and organs were stored for cytokines measurements. ResultsDespite similar lung and hemodynamic findings, the administration of IgM-enriched immunoglobulins compared to placebo significantly modulates the inflammatory response by increasing IL-10 levels in the bloodstream and by decreasing TNF-α in bronchoalveolar lavage (BAL) fluid. Furthermore, in vitro data suggest that IgM-enriched immunoglobulins induce monocytes production of IL-10 after LPS stimulation. ConclusionsIn an in vivo model of pneumonia developing shock, IgM-enriched immunoglobulins administered as rescue treatment enhance the anti-inflammatory response by increasing blood levels of IL-10 and reducing TNF-α in BAL fluid.

Anesthetic postconditioning plus hypothermia following cardiopulmonary resuscitation protects the myocardial ultrastructure by modulating inflammatory events in rabbits

Myocardial ischemia/reperfusion (I/R) injury is usually caused by resuscitation following cardiac arrest. The aim of the present study was to investigate the influence of sevoflurane postconditioning on the myocardial ultrastructure induced by cardiac arrest and successful resuscitation in mature rabbits. A total of 32 rabbits were randomly and equally divided into an I/R group (I/R group), a hypothermia group (H group), a sevoflurane postconditioning group (S group), and hypothermia plus sevoflurane postconditioning group (H + S group). Interleukin (IL)-8 and IL-10 levels in blood were evaluated at four different time points (1 h pre-ischemia: T1; 1, 2 and 3 h after reperfusion: T2, T3 and T4, respectively). The myocardial ultrastructure was evaluated by microscope after the rabbits were scarified. Plasma levels of IL-8 and IL-10 increased in all of the groups from T2. However, compared with the I/R group from T3 and T4, downregulation of IL-8 was significant in the S and H + S groups (P<0.05), and the result of intra-group comparison demonstrated that the level of serum IL-8 was the lowest in the H + S group (P<0.05). By contrast, upregulation of IL-10 was significantly higher in the S and H + S groups (P<0.05), particularly in the H + S group. Notably, ultrastructure damage of the myocardium was significantly lighter, and the structural integrity of the myocardium in the H + S group was better when compared with that of the S group. Thus, sevoflurane postconditioning plus hypothermia protected the myocardial ultrastructure following cardiopulmonary resuscitation by suppressing inflammatory effects.

IL-10-592 polymorphism is associated with IL-10 expression and severity of enterovirus 71 infection in chinese children

BackgroundEnterovirus 71 (EV71) infection results in some severe complications with high mortality and disability in Hand, Foot and Mouth Disease (HFMD) in children. Recent studies have shown that cytokine genetic predispositions have associations with both the development of EV71 infection and severity of HFMD. ObjectiveThis study was designed to investigate whether the IL-10–592 polymorphism is associated with IL-10 levels and disease severity in Chinese children with EV71 infection. Study designIn patients selected, there were 378 cases with EV71 infection (including 291 mild cases, 70 severe cases and 17 critical cases), as well as 406 health controls. EV71 in serum was tested by RT-PCR, and IL-10-592 genotype was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis techniques. ResultThe IL-10-592C allele was observed with higher frequency in patients with critical EV71 infection (70.59%) compared with severe EV71 infection (41.43%, P<0.01), mild EV71 infection (43.81%, P<0.01) and healthy children (44.46%, P<0.01). The blood IL-10 levels of critical cases were significantly higher than severe cases, mild cases, and healthy children. Among all of the four groups, IL-10 levels in patients with genotype AA were significantly lower than those with genotypes AC+CC (t=4.86, P<0.05; t=2.30, P<0.05; t=3.44, P<0.05; t=5.58, P<0.05). ConclusionIL-10-592C allele is associated with IL-10 expressions and the severity of EV71 infection in Chinese patients.

Anesthesia and Surgery Impair Blood-Brain Barrier and Cognitive Function in Mice.

Blood–brain barrier (BBB) dysfunction, e.g., increase in BBB permeability, has been reported to contribute to cognitive impairment. However, the effects of anesthesia and surgery on BBB permeability, the underlying mechanisms, and associated cognitive function remain largely to be determined. Here, we assessed the effects of surgery (laparotomy) under 1.4% isoflurane anesthesia (anesthesia/surgery) for 2 h on BBB permeability, levels of junction proteins and cognitive function in both 9- and 18-month-old wild-type mice and 9-month-old interleukin (IL)-6 knockout mice. BBB permeability was determined by dextran tracer (immunohistochemistry imaging and spectrophotometric quantification), and protein levels were measured by Western blot and cognitive function was assessed by using both Morris water maze and Barnes maze. We found that the anesthesia/surgery increased mouse BBB permeability to 10-kDa dextran, but not to 70-kDa dextran, in an IL-6-dependent and age-associated manner. In addition, the anesthesia/surgery induced an age-associated increase in blood IL-6 level. Cognitive impairment was detected in 18-month-old, but not 9-month-old, mice after the anesthesia/surgery. Finally, the anesthesia/surgery decreased the levels of β-catenin and tight junction protein claudin, occludin and ZO-1, but not adherent junction protein VE-cadherin, E-cadherin, and p120-catenin. These data demonstrate that we have established a system to study the effects of perioperative factors, including anesthesia and surgery, on BBB and cognitive function. The results suggest that the anesthesia/surgery might induce an age-associated BBB dysfunction and cognitive impairment in mice. These findings would promote mechanistic studies of postoperative cognitive impairment, including postoperative delirium.

Leptin and interleukin-6 level in patients with hypertension and obesity combined with non-alcoholic steatohepatitis during treatment with sartans and statins

Abstract The results of treatment of patients with arterial hypertension and obesity combined with non-alcoholic steatohepatitis are presented in article. Herein, the combined use of olmesartan or telmisartan with atorvastatin for 12 weeks had a positive impact on the physical condition of patients with arterial hypertension and obesity. This effect was manifested by maintenance of optimal blood pressure, the reduction of subjective complaints and the improvement of heart hemodynamics. Administration of sartans and statins to patients with arterial hypertension combined with obesity and non-alcoholic steatohepatitis led to a significant reduction of LDL (p&lt;0.01) and LDL cholesterol levels (p&lt;0.01), as well as the values of leptin (p&lt;0.01) and IL-6 (p&lt;0.01). The combination of olmesartan or telmisartan with atorvastatin not only allows a control of BP, but also a reduction of the pro-atherogenic fractions of blood lipids, hyperleptinaemia and levels of pro-inflammatory IL-6, hence, in this manner, improving the patient general condition.

Can Recombinant Granulocyte Colony Stimulating Factor Modulate Inflammatory Response in Extreme Low Gestational Age Newborns?: Effect of rhG-CSF on Cytokines in ELGAN

Background Elevated levels of cytokines like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) are common in critically ill neonates, and may contribute to organ-based injury during acute illness contributing to neurodevelopmental delay. In both animals and human adults, recombinant human granulocyte-colony stimulating factor (rhG-CSF) is associated with a reduction in TNF-α blood levels. Objective We aim to determine whether rhG-CSF treatment affects the blood levels of proinflammatory cytokines, TNF-α and IL-6 or the anti-inflammatory cytokine, IL-10 in extremely-low-gestational age neonates (ELGANs) compared with conventional medical management. Methods The study included three groups of ELGANs between 2 and 4 days of age as subjects. Control group (n = 5); treated, nonseptic group (n = 10); and treated, septic group (n = 5) neonates were treated with conventional measures. In addition, the test subjects were treated with 10 μg/kg/d of rhG-CSF intravenously for 3 consecutive days. The levels of TNF-α, IL-6, and IL-10 were measured before and 24 hours after completion of the study. Results The average TNF-α levels increased after birth in control subjects but did not rise in rhG-CSF treated subjects. A nonsignificant decrease of IL-6 and IL-10 blood levels was noted in all the subjects independent of the drug treatment. Conclusion The use of rhG-CSF is associated with lower TNF-α levels in ELGANs. Speculation During critical illness or sepsis, rhG-CSF may have unanticipated benefits as a drug that can elevate neutrophil number and function in neonates while simultaneously limiting collateral injury due to TNF-α.

Research of the clinical effect and immune regulatory mechanism of red blue light combined with Niuhuang-Shangqing capsules for the moderate-severe acne

Objective To investigate the the clinical effect and immune regulatory mechanism of red-blue light combined with Niuhuang Shangqing capsules for the moderate-severe acne. Methods A total of 180 patients with moderate to severe acne treated in People’s Hospital of Nanhai District in Foshan City from June 2014 to June 2016 were randomly divided into 2 groups with each group 90 patients. The control group was treated with red and blue light, and observation group was treated with the combination of red and blue light and Niuhuang-Shangqing capsules. The levels of SP (Substance P), IL-1 and IL-6 in peripheral blood were observed and analyzed. The recurrence rates and adverse events were observed. Results After treatment, the SP (657.4 ± 36.6 pg/ml vs. 799.9 ± 60.2 pg/ml, t=19.188), IL-1(61.8 ± 24.7 pg/L vs. 92.1 ± 23.5 pg/L, t=8.431), IL-6 (38.7 ± 10.3 pg/ml vs. 66.7 ± 14.1 pg/ml, t=12.421) of the observation group were significantly better than those of the control group (all Ps<0.01). The total effect rate of the observation group were 91.11% (82/90), which were significantly higher than 70.00% (63/90) of control group (χ2=12.804, P<0.01). Conclusions The Red-blue light combined with Niuhuang-Shangqing capsules for treating moderate-severe acne, has significant effect and can reduce the serum levels of SP, IL-1 and IL-6, with fewer adverse events and lower recurrence rates. They can be used as a safe and effective treatment of acne. Key words: Acne vulgaris; Color therapy; Niu Huang Shang Qing capsule; Adjuvants, immunologic; Comparative effectiveness research

Circulating blood levels of IL-6, IFN-\u03b3, and IL-10 as potential diagnostic biomarkers in gastric cancer: a controlled study

BackgroundGastric adenocarcinoma is the third most common cause of cancer-associated death worldwide. Helicobacter pylori infection activates a signaling cascade that induces production of cytokines and chemokines involved in the chronic inflammatory response that drives carcinogenesis. We evaluated circulating cytokines and chemokines as potential diagnostic biomarkers for gastric cancer.MethodsWe included 201 healthy controls and 162 patients with distal gastric cancer who underwent primary surgical resection between 2009 and 2012 in Mexico City. The clinical and pathological data of patients were recorded by questionnaire, and the cancer subtype was classified as intestinal or diffuse. Pathological staging of cancer was based on the tumor–node–metastasis staging system of the International Union Against Cancer. Concentrations of IL-1β, IL-6, TNF-α, IL-10, and MCP-1 in serum were measured using multiplex analyte profiling technology and concentrations of IL-8, IFN-γ, and TGF-β in plasma were measured using enzyme-linked immunosorbent assay.ResultsLevels of IL-1β, IL-6, IFN-γ, and IL-10 were significantly higher and that of MCP-1 was lower in gastric cancer patients compared with controls. No differences in IL-8 or TNF-α levels were observed between gastric cancer and controls. IFN-γ and IL-10 were significantly higher in both intestinal and diffuse gastric cancer, whereas IL-1β and IL-6 were higher and TGF-β lower only in intestinal gastric cancer; MCP-1 was lower only in diffuse gastric cancer. IFN-γ and IL-10 levels were significantly higher in early (I/II) and late stage (III/IV) gastric cancer; IL-1β and IL-8 were higher and MCP-1 was lower only in late stage (IV) patients. Receiver-operating characteristic analysis showed that for diagnosis of GC, IL-6 had high specificity (0.97) and low sensitivity (0.39), IL-10 had moderate specificity (0.82) and low sensitivity (0.48), and IL-1β and IFN-γ showed low specificity (0.43 and 0.53, respectively) and moderate sensitivity (0.76 and 0.71, respectively).ConclusionsIncreased levels of IL-6, IFN-γ, and IL-10 might be useful as diagnostic biomarkers for GC; however, this needs to be confirmed with larger number of patients and with control groups other than blood donors, properly age paired. IL-1β, IL-6, MCP-1, and TGF-β differentiate intestinal from diffuse GC. IFN-γ and IL-10 might be useful for diagnosis of early stage GC, and IL-1β, IL-8, and MCP-1 for late stages of the disease.