Increase In Concentration Of IL-10 Research Articles

Maternal Obesity Causes Sex Specific Long-Term Hematopoietic and Metabolic Defects

Maternal obesity is increasingly common and can negatively impact offspring health. Children born to obese mothers are at higher risk of developing diseases involved with metabolic health (e.g., type 2 diabetes). Many of these diseases are associated with abnormalities within the hematopoietic system such as atypical immune profiles or hematopoiesis. Interestingly, disease incidence and/or severity is often dependent on the offspring's gender. This suggests that there may be sex-specific reprogramming of hematopoietic stem and progenitor cells (HSPCs) during immune cell development. This study aims to test the hypothesis that offspring of obese mice exhibit sex-differences in HSPC function that affect offspring's metabolic health. To test this, C57BL/6 (CD45.2+) dams were fed standard chow (2018SX, Envigo, IN) or western-style diet (TD.88137, Envigo, IN) for four weeks prior to mating, through pregnancy, and the lactating period. At postnatal day 21, HSPCs (Lineage negative, Sca1 positive, cKit positive cells) were flow-sorted from bone marrow (BM) of offspring from dams fed chow (Con) or western-style diet (MatOb) and used for competitive transplant (Boy/J BM competitor cells; CD45.1+) into same-sex lethally irradiated C57BL/6 x Boy/J F1 (CD45.1+CD45.2+) recipient mice (8-10 weeks of age) or for RNA-sequencing analysis. Secondary transplants were performed to look at long-term engraftment potential of HSPCs. Body weight, body adiposity, fasting insulin, glucose tolerance test (GTT), and pancreatic β and α-cell area were assessed on male and female recipients of both primary and secondary transplants. Compared to mice that received male Con HSPCs, recipient mice that received male MatOb HSPCs had significantly lower donor chimerism in the blood and BM post-secondary transplantation. This was associated with a significant reduction in donor hematopoietic stem cell (HSC) numbers in the BM 16 weeks post-secondary transplant, indicating male MatOb HSPCs had decreased long-term engraftment capability due to an exhaustion of the HSC pool. This reduction in HSPC engraftment seen between male MatOb versus Con HSPCs was not seen when using HSPCs from female offspring. Next, metabolic parameters of our recipient mice was examined. Sixteen weeks after primary transplant, there were no differences detected in body weight and adiposity in the Con and MatOb HSPC recipient mice. Compared to sex-matched controls, we found that recipients transplanted with male MatOb HSPCs developed glucose intolerance, increased fasting serum insulin concentrations, and decreased β-cell area, supporting the presence of impaired glucose metabolism due to a combination of insulin resistance and lower β-cell mass. There was no difference in recipients of HSPCs from female Con and female MatOb pups. RNA-seq of BM HSPCs at time of transplant (p21) from Con or MatOb revealed 100 differentially expressed genes (DEG) in male MatOb HSPCs and 1788 DEG in female MatOb HSPCs. There were more and higher magnitude of differential gene expression in female mice than male, despite the long-term phenotypic differences being evident in males but not females, and the majority of genes changed in males were also altered in females. This suggests that the gene programs responsible for the observed phenotypes may be altered by maternal obesity in both male and female offspring, but that female offspring have a transcriptomic profile that confers protection on the HSPC population. One of the most striking findings from the transcriptomic analysis was a marked enrichment in gene programs associated with immune response, interferon signaling, and cytokine production in female MatOb offspring compared to sex matched controls that is not seen in male MatOb offspring. Pathway analysis identified upregulation of programs involving both IFNγ and IL-10 in the female MatOb HSPCs when compared to sex-mated Con HSPCs which correlated with an increase in IL-10 concentrations in the serum of p21 female MatOb mice. These pathways were downregulated or unaltered in males with no change in systemic IL-10 concentration.Our results demonstrate that maternal obesity results in sex-specific changes in offspring HSPC function and a novel role HSPCs may play in regulating glucose metabolism in the offspring of obese dams.

Interleukin 12 in the Acute Phase of the Immune Response after Excimer Laser Treatment.

The aim of the research was to investigate the differences in the concentrations of IL-12, IL-4, IL-10, and IFN-γ in tears after LASIK and PRK procedures. The study included 68 myopic eyes up to -3.0 D refractive spherical equivalent, divided into two groups: Group 1 LASIK (n = 31) and Group 2 PRK (n = 37). Three tear samples were taken from each eye: immediately before the procedure (t0), 1 h after the procedure (t1), and 24 h after the procedure (t2). The concentrations of IL-12p70, IL-4, IL-10, and IFN-γ in the tear samples were determined by flow cytometry. Participants were not taking anti-inflammatory therapy 24 h after the procedure. IL-4 levels 1 h after treatment did not differ between LASIK and PRK (p = 0.990), while 24 h after PRK there was a significant decrease in IL-4 levels (p < 0.05), but not after LASIK (p = 0.476). In both the LASIK (p < 0.05) and PRK (p < 0.05) groups, there is an increase in IL-10 concentrations 1 h after treatment, which persists 24 h after LASIK (p < 0.05) but not after PRK (p = 0.081). There is an increase in IL-12p70 concentration 1 h after treatment in both the LASIK (p < 0.001) and PRK groups (p < 0.001). There is also an increase in IL-12p70 concentration 24 h after PRK (p < 0.005), but not after LASIK (p = 0.775). IL-4 concentration shows a significantly higher value in the LASIK group than in the PRK group after 24 h. IL-10 and IL-12p70 levels increase one hour after surgery in both groups. After 24 h, the IL-10 levels remain elevated in the LASIK group, and the IL-12p70 levels remain elevated in the PRK group. Thus, LASIK and PRK procedures show different inflammatory dynamics.

The effects of a single and a series of Finnish sauna sessions on the immune response and HSP-70 levels in trained and untrained men

Background The aim of the study was to investigate the effect of a Finnish sauna on the immune status parameters. The hypothesis was that hyperthermia would improve immune system’s functioning by changing the proportion of lymphocyte subpopulations and would activate heat shock proteins. We assumed that the responses of trained and untrained subjects would be different. Material and methods Healthy men (20–25 years old) were divided into groups: the trained (T; n = 10), and the untrained group (U; n = 10). All participants were subjected to 10 baths (each one consisted of: 3 × 15-minute exposure with cooled down for 2 min. Body composition, anthropometric measurements, VO2 peak were measured before 1st sauna bath. Blood was collected before the 1st and 10th sauna bath, and 10 min after their completion to asses an acute and a chronic effect. Body mass, rectal temperature and heart rate (HR) were assessed in the same time points. The serum levels of cortisol, Il-6, HSP70 were measured with use of ELISA method, IgA, IgG and IgM by turbidimetry. White blood cells (WBC), leukocyte populations counts: neutrophils, lymphocytes, eosinophils, monocytes, and basophils were determined with use of flow cytometry as well as T-cell subpopulations. Results No differences were found in the increase in rectal temperature, cortisol and immunoglobulins between groups. In response to the 1st sauna bath, a greater increase in HR was observed in the U group. After the last one, the HR value was lower in the T group. The impact of sauna baths on WBC, CD56+, CD3+, CD8+, IgA, IgG and IgM was different in trained and untrained subjects’ responses. A positive correlation between the increase in cortisol concentrations and increase in internal temperatures after the 1st sauna was found in the T (r = 0.72) and U group (r = 0.77), between the increase in IL-6 and cortisol concentrations in the T group after the 1st treatment (r = 0.64), between the increase in IL-10 concentration and internal temperature (r = 0.75) and between the increase in IL-6 and IL-10 (r = 0.69) concentrations, also. Conclusions Sauna bathing can be a way to improve the immune response, but only when it is undertaken as a series of treatments.

Cytokine markers of clinical variants of infective endocarditis

Introduction. Infective endocarditis is a bacterial disease. Pathogen is localized mainly on heart valves and endocardium. This condition is accompanied by immunopathological manifestations and potential generation of septic process being unfavorable prognosis for disease outcome. Currently, the causes of death of patients with endocarditis have been increasingly presented as thromboembolic complications, which severity depends on variant of the disease course. An important role in imbalanced immune system in the infectious process is assigned to altered intercellular interaction mediated via cytokine network. Activated immune cells produce cytokines, which investigating is important in terms of interpreting changes in immune system functionality, assessing the severity of diseases and controlling therapeutic effectiveness. Infective endocarditis remains a severe disease associated with high mortality despite current advances in diagnostics and treatment. A timely diagnostic process and early initiation of treatment are major factors for successful patient management necessitating to improve diagnostics of various clinical variants of endocarditis course, taking into account pathogenetically relevant cytokines. Objective was to comparatively evaluate the importance of serum cytokine concentrations in patients with uncomplicated course of infective endocarditis and its thromboembolic complications and determine cytokine markers of various variants of endocarditis course. Materials and methods. An immunological examination of 119 blood serum samples from patients with confirmed diagnosis of infectious endocarditis and 20 samples from apparently healthy persons was carried out. Depending on the clinical disease form, the patients were divided into 4 groups: group 1 primary infective endocarditis (PIE) with thromboembolic complications (n = 24), 2 PIE without thromboembolic complications (n = 34), 3 secondary IE with thromboembolic complications (n = 27), 4 secondary IE without thromboembolic complications (n = 34). The control group consisted of 20 apparently healthy subjects. Immunological studies of serum cytokine concentrations were conducted in all groups. Results. Statistically significant increase in serum concentration of IL-10, IL-6, VEGF-A, IL-18, IL-1Ra and IL-8 was revealed in all clinical groups of patients compared to those in control group (p 0,05). By correlation analysis, we found a significant positive relationship between IL-10 and IL-18 or IL-6. An increase in the concentration of IL-10 leads to increased level of pro-inflammatory IL-18 and IL-6. The marker of secondary endocarditis was observed as increased level of serum concentrations of IFN. A characteristic feature of primary infective endocarditis with thromboembolic complications was revealed as significantly increased serum concentration of IL-8, IL-1Ra and IL-6. Markers of secondary complicated endocarditis were identified as increased level of IL-6, VEGF-A and IL-18.

Effects of photobiomodulation and a physical exercise program on the expression of inflammatory and cartilage degradation biomarkers and functional capacity in women with knee osteoarthritis: a randomized blinded study

BackgroundThe knee osteoarthritis (OA) is a joint disease characterized by degradation of articular cartilage that leads to chronic inflammation. Exercise programs and photobiomodulation (PBM) are capable of modulating the inflammatory process of minimizing functional disability related to knee OA. However, their association on the concentration of biomarkers related to OA development has not been studied yet. The aim of the present study is to investigate the effects of PBM (via cluster) with a physical exercise program in functional capacity, serum inflammatory and cartilage degradation biomarkers in patients with knee OA.MethodsForty-two patients were randomly allocated in 3 groups: ESP: exercise + sham PBM; EAP: exercise + PBM and CG: control group. Six patients were excluded before finished the experimental period. The analyzed outcomes in baseline and 8-week were: the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) and the evaluation of serum biomarkers concentration (IL-1β, IL-6, IL-8, IL-10 e TNF-α, and CTX-II).ResultsAn increase in the functional capacity was observed in the WOMAC total score for both treated groups (p < 0.001) and ESP presents a lower value compared to CG (p < 0.05) the 8-week post-treatment. In addition, there was a significant increase in IL-10 concentration of EAP (p < 0.05) and higher value compared to CG (p < 0.001) the 8-week post-treatment. Moreover, an increase in IL-1β concentration was observed for CG (p < 0.05). No other difference was observed comparing the other groups.ConclusionOur data suggest that the physical exercise therapy could be a strategy for increasing functional capacity and in association with PBM for increasing IL-10 levels in OA knee individuals.Trial registration: ReBEC (RBR-7t6nzr).

Multiple sclerosis and immune system biomarkers: Novel comparison in glatiramer acetate and interferon beta-1a-treated patient groups

BackgroundMultiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS). T cells and B lymphocytes are involved in the development of this disease. MethodsThe following biomarkers were determined in peripheral blood in 28 patients treated with glatiramer acetate (GA) and 21 patients treated with interferon beta 1-a (IFN): IL-10, BAFF, Mx1, IgG, IgG1, IgG2, IgG3 and IgG4 (at baseline and after 6 months of treatment). All participants had confirmed MS diagnosis. ObjectivesThe primary objective is to assess a percentual change of biomarkers after 6 months since the first-line treatment initiation with GA or IFN. The secondary objective is to explore correlations between the baseline biomarkers‘ values (levels). ResultsA positive trend was observed in the increase in IL-10 concentration by 30.33 % (IFN) and by 15.65 % (GA). In the IFN group, we observed a statistically significant increase in the BAFF protein concentration by 29.9% (P < 0.001). We found that Mx1 protein levels did not change with the administration of GA, which can be explained by the different mechanisms of action of GA. The serum levels of IgG immunoglobulins and both IgG1 and IgG4 subclasses in both groups of patients were increased. Thus, our data were in accordance with the generally accepted assumption that both IFN and GA are capable of modulating the B cell system. ConclusionsOur results suggest that treatment with IFN and GA has a more pronounced influence on the B cell system of MS.

Ameliorative effect of 2-methoxyestradiol on radiation-induced lung injury

AimsRadiation-induced lung injury (RILI) is a serious complication of radiation therapy. Development of an effective drug that selectively protects normal lung tissues and sensitizes tumor cells to radiotherapy is an unmet need. 2-Methoxyestradiol (2ME2) possesses polypharmacological properties, which qualifies it as an effective radioprotector. Our aim is to explore the potential protective effects of 2ME2 against early and late stages of RILI and the underlying mechanisms. Main methodsBALB/c mice were either treated with 2ME2 (50 mg/kg/day i.p., for 4 weeks); or received a single dose of 10 Gy ionizing radiation (IR) delivered to the lungs; or 10 Gy IR and 2ME2. Animal survival and pulmonary functions were evaluated. Immune-phenotyping of alveolar macrophages (AM) in the broncho-alveolar lavage fluids (BALF) was determined by flow cytometry. ELISA was used to evaluate the expression levels of TNF-α, TGF-β; and IL-10 in BALF. Lung tissues were used for histopathological examination or immunofluorescence staining for CD68 (pan-macrophage marker), Arginase-1 (Arg1, M2-specific marker), inducible nitric oxide synthase (iNOS, M1-specific marker) and HIF-1α. VEGF and γH2AX expression in lung tissues were detected by western blot. Key findingsThe results demonstrated that 2ME2 improved the survival, lung functions and histopathological parameters of irradiated mice. Additionally, it attenuated the radiation-induced AM polarization and reduced the pneumonitis and fibrosis markers in lung tissues. Significant reduction of TNF-α and TGF-β with concomitant increase in IL-10 concentrations were observed. Moreover, the expression of HIF-1α, VEGF and γH2AX declined. Significance2ME2 is a promising radioprotectant with fewer anticipated side effects.

Dynamics of background levels of serum cytokines in children with atopic dermatitis with concomitant pathology of oral mucosa in the course of optimized complex therapy

Dynamics of background levels of serum cytokines in children with atopic dermatitis with concomitant pathology of oral mucosa in the course of optimized complex therapy

The effect of probiotics on inflammatory biomarkers: a meta-analysis of randomized clinical trials

No study has summarized earlier findings on the effect of probiotic supplementation on inflammatory biomarkers. This systematic review and meta-analysis was conducted to systematically review the available placebo-controlled clinical trials about the effect of probiotic supplementation on several inflammatory biomarkers in adults. Relevant papers published up to March 2018 were searched up through PubMed, MEDLINE, SCOPUS, EMBASE, and Google Scholar, using following suitable keywords. Clinical trials that examined the effect of probiotic supplementation on inflammation in adults were included. Overall, 42 randomized clinical trials (1138 participants in intervention and 1120 participants in control groups) were included. Combining findings from included studies, we found a significant reduction in serum hs-CRP [standardized mean difference (SMD) - 0.46; 95% CI - 0.73, - 0.19], TNF-a (- 0.21; - 0.34, - 0.08), IL-6 (- 0.37; - 0.51, - 0.24), IL-12 (- 0.47; - 0.67, - 0.27), and IL-4 concentrations (- 0.48; - 0.76, - 0.20) after probiotic supplementation. Pooling effect sizes from 11 studies with 12 effect sizes, a significant increase in IL-10 concentrations was seen (0.21; 0.04, 0.38). We failed to find a significant effect of probiotic supplementation on serum IL-1B (- 0.17; - 0.37, 0.02), IL-8 (- 0.01; - 0.30, 0.28), and IFN-g (- 0.08; - 0.31, 0.15) and IL-17 concentrations (0.06; - 0.34, 0.46). Probiotic supplementation significantly reduced serum concentrations of pro-inflammatory cytokines including, hs-CRP, TNF-a, IL-6, IL-12, and IL-4, but it did not influence IL-1B, IL-8, IFN-g, and IL-17 concentrations. A significant increase in serum concentrations of IL-10, as a anti-inflammatory cytokine was also documented after probiotic supplementation.

Ultra-endurance Triathlon Performance And Markers Of Whole-body And Gut-specific Inflammation

PURPOSE: To examine the influence of the Ultraman triathlon (3 days of non-continuous racing; stage 1: 10 km swim and 144.8 km cycle; stage 2: 275.4 km cycle; stage 3: 84.4 km run) on circulating plasma concentrations of whole-body (CRP, IL-6, and IL-10) and gut-specific inflammatory markers (IL-17 and IL-23) in trained participants (N = 17; 14 men, 3 women), and determine whether these variables influence performance. METHODS: Fourteen triathletes (age: 39 ± 8 yrs) were evaluated pre-race and post-race for circulating concentrations of CRP, IL-6, IL-10, IL-17, and IL-23. Blood samples were drawn two days prior to stage 1 (1600 h) and one day after stage 3 (1200 h). Plasma biomarker concentrations were determined by ELISA according to manufacturer’s instructions. Data were analyzed with SPSS and significance was accepted at p < 0.05. Values are reported as means ± SD. Data points (for blood biomarkers) greater than 2 SD from the mean were removed as outliers. RESULTS: Plasma CRP significantly increased from pre-race (266.27 ± 276.18 ng/mL) to post-race (25,891.94 ± 12,888.65 ng/mL; p < 0.001). Plasma IL-10 increased from pre-race (3.46 ± 2.98 pg/mL) to post-race (5.15 ± 1.89 pg/mL). Pre-race concentrations of IL-6 were below detectable limits; post-race IL-6 concentrations were 4.00 ± 3.74 pg/mL. Both pre-race and post-race concentrations of IL-17 and IL-23 were below detectable limits. Pearson’s correlation between mean finish time and post-race CRP and post-race IL-10 was 0.35 and 0.54 (p < 0.05), respectively. CONCLUSIONS: The significant increase in CRP during the race may have been due to muscle damage. The greater anti-inflammatory capacity of the athletes likely led to increased clearance of IL-6, IL-17, and IL-23 the day after the race; the increase in IL-10 concentrations during the race reflect this anti-inflammatory response. A significant positive correlation between post-race IL-10 concentrations and mean finish time may indicate that a relationship between anti-inflammatory responses and performance exists. This study was supported by Florida State University.

Effects of interleukin-10 gene polymorphism on clinical diversity and activity of systemic lupus erythematosus

This study was carried out to determine the effects of interleukin (IL)-10 gene polymorphism 1082A/G on clinical diversity and activity of systemic lupus erythematosus (SLE), as it was shown to be associated with E26 transcription factor binding site, and to assess IL-10 concentration in SLE patients. Blood was drawn from 54 SLE patients and 27 healthy controls for DNA extraction. The single nucleotide polymorphism was identified using the PCR-restriction fragment length polymorphism, and serum sample was collected to assay IL-10 concentration. There was an increase in IL-10 concentration in SLE total patients (mean 49.5 pg/ml). Mutant allele A (76.9%) was found more frequently in SLE patients compared with allele G (23.1%). Genotype AA (66.7%) was found more frequently, followed by AG (20.4%) and GG (12.9%). IL-10 concentration was elevated in SLE patients and was shown to be associated with disease activity. IL-10 gene polymorphism is not a strong indicator to show susceptibility of the disease.

Inflammation-mediating cytokine response to acute handcycling exercise with/without functional electrical stimulation-evoked lower-limb cycling.

This feasibility study compared the plasma inflammation-mediating cytokine response to an acute bout of handcycling (HC) with and without the addition of functional electrical stimulation (FES)-evoked lower-limb cycling. On two separate occasions, five recreationally active, community-based participants with motor complete paraplegia (thoracic 5- 7) performed 30 min HC and hybrid exercise (HYB) at a fixed power output. Venous blood samples were collected at rest, immediately postexercise, 1 h postexercise (post+1) and 2 h postexercise (post+2). Plasma interleukin (IL)-6, IL-10, IL-1 receptor antagonist (IL-1ra), adrenaline, and cortisol concentrations were determined via enzyme-linked immunoassay. Plasma IL-6 concentrations were significantly (p < 0.04) elevated (~2.5-fold) at post+1 and post+2 in HYB only. A small (0.5-fold), nonsignificant (p > 0.05) increase in IL-6 was observed at post+1 in HC, with concentrations significantly higher in HYB at post+2 (p < 0.02). Plasma IL-1ra was unaffected in both trials. Although not reaching statistical significance (p = 0.15), a ~1-fold increase in IL-10 concentration was seen in HYB at post+2. In contrast, increases in adrenaline (p < 0.04) and cortisol (p = 0.08) were observed immediately postexercise in HC and HYB. Initial findings suggest paralyzed skeletal muscle releases IL-6 in response to FES-evoked contractions. HYB may provide a greater anti-inflammatory potential in individuals with a thoracic spinal cord injury compared with HC alone.

In vitro effects of CpG oligodeoxynucleotides delivered by gelatin nanoparticles on canine peripheral blood mononuclear cells of atopic and healthy dogs – a pilot study

Cytosine-phosphate-guanine (CpG) oligodeoxynucleotides offer a novel promising immunotherapeutic approach for atopic dermatitis (AD) both in humans and animals. Gelatin nanoparticles (GNP) enhance and prolong CpG-associated immunomodulatory effects and minimize adverse effects both in vitro and in vivo. Information about the effects of this combination in dogs is lacking. The aim of this study was to evaluate immunological effects of CpG coupled to GNP on canine peripheral blood mononuclear cells (PBMCs) in vitro. Eight dogs with AD, diagnosed by standard criteria and with a concurrent immediate hypersensitivity to house dust mites were included. Control samples were taken from eight healthy, age-matched control dogs without history or evidence of cutaneous or systemic illness. Peripheral blood mononuclear cells of healthy and allergic dogs were incubated with CpG-GNP and the uptake of CpG-GNP was demonstrated using confocal laser scanning microscopy. Cell culture supernatant concentrations of interferon gamma (IFN-γ), interleukin (IL)-4, IL-6 and IL-10 were measured by Canine Cytokine Milliplex. No significant changes in IFN-γ and IL-4 were found when comparing PBMCs incubated with CpG and CpG-GNP with the negative controls in atopic and healthy dogs. Interleukin-6 was not detected in any of the groups. However, a statistically significant increase in IL-10 concentration was found after 24h stimulation with CpG-GNP compared with CpG alone both in atopic and healthy dogs. As IL-10 is considered an immunosuppressive cytokine playing a key role in peripheral tolerance; the reported CpG-GNP formulation could be a new approach in allergy treatment.

Immunomodulatory and protective effect of probiotic Lactobacillus casei against Candida albicans infection in malnourished mice

The effect of Lactobacillus casei CRL 431 (Lc), when administered as a supplement to a repletion diet, on the resistance of malnourished mice to Candida albicans infection was studied. Weaned mice were malnourished by being given a protein-free diet (PFD) for 21 days. The malnourished mice were then fed a balanced conventional diet (BCD) for 7 days or BCD for 7 days with supplemental Lc on days 6 and 7 (BCD+Lc). Malnourished (MNC) and well-nourished (WNC) mice were used as controls. At the end of the treatments the mice were infected intraperitoneally with C. albicans. Animals that had received probiotics had improved survival and resistance against this infection compared to those in the BCD and MNC groups. The number and fungicidal activity of phagocytes, and the concentrations of tumor necrosis factor-α, interferon-γ and interleukin-6 (IL-6), increased in blood and infected tissues in all experimental groups, but MNC mice showed lower concentrations than those in the WNC group. BCD and BCD+Lc mice showed higher concentrations of these variables than those in the MNC group, but only the BCD+Lc group presented values similar to the WNC mice. Malnutrition also impaired the production of IL-17 and IL-10 in response to infection. Both repletion treatments normalized IL-17 concentrations, but IL-10 in the BCD+Lc group was significantly higher than in WNC mice. The addition of L. casei to the repletion diet normalized the immune response against C. albicans, allowing efficient recruitment and activation of phagocytes, as well as effective release of pro-inflammatory cytokines. In addition, probiotic treatment induced an increase in IL-10 concentrations, which would have helped to prevent damage caused by the inflammatory response.

Dose-Dependent Immunomodulation of Human Dendritic Cells by the Probiotic Lactobacillus rhamnosus Lcr35

The response of the immune system to probiotics remains controversial. Some strains modulate the cytokine production of dendritic cells (DCs) in vitro and induce a regulatory response, while others induce conversely a pro-inflammatory response. These strain-dependent effects are thought to be linked to specific interactions between bacteria and pattern recognition receptors. We investigated the effects of a well characterized probiotic strain, Lactobacillus rhamnosus Lcr35, on human monocyte-derived immature DCs, using a wide range of bacterial concentrations (multiplicity of infection, MOI, from 0.01 to 100). DNA microarray and qRT-PCR analysis showed that the probiotic induced a large-scale change in gene expression (nearly 1,700 modulated genes, with 3-fold changes), but only with high doses (MOI, 100). The upregulated genes were mainly involved in immune response and identified a molecular signature of inflammation according to the model of Torri. Flow cytometry analysis also revealed a dose-dependent maturation of the DC membrane phenotype, until DCs reached a semi-mature state, with an upregulation of the membrane expression of CD86, CD83, HLA-DR and TLR4, associated with a down-regulation of DC-SIGN, MR and CD14. Measurement of the DC-secreted cytokines showed that Lcr35 induced a strong dose-dependent increase of the pro-Th1/Th17 cytokine levels (TNFα, IL-1β, IL-12p70, IL-12p40 and IL-23), but only a low increase in IL-10 concentration. The probiotic L. rhamnosus Lcr35 therefore induce a dose-dependent immunomodulation of human DCs leading, at high doses, to the semi-maturation of the cells and to a strong pro-inflammatory effect. These results contribute to a fuller understanding of the mechanism of action of this probiotic, and thus of its potential clinical indications in the treatment of either infectious or IgE-dependent allergic diseases.

Analysis of peripheral blood lymphocyte phenotypes and Th1/Th2 cytokines profile in the systemic immune responses ofHelicobacter pyloriinfected individuals

H. pylori elicits specific humoral and cellular immune responses in the mucosal immune system. However, the type and extent of T lymphocyte response in the systemic immune system is not clear for H. pylori positive patients. In this study, peripheral blood T lymphocyte phenotypes and serum Th1/Th2 based cytokines of 32 H. pylori positive patients were analyzed and compared to those of healthy controls. While alphabeta TCR(+) lymphocytes and their phenotype analysis were not significantly different to those of healthy controls, the percentage of pan gammadelta TCR(+) lymphocytes was up to 2.4 times greater in the H. pylori positive group then in healthy controls. Furthermore, significant increases in IL-10 concentrations in serum samples of H. pylori patients indicated that their immune systems had switched toward a Th2 type immune response. The correlation between phenotype and type of T cell response in the peripheral blood during H. pylori infection is discussed.

Prevention of changes in airway function facilitates Strongyloides venezuelensis infection in rats

Alterations in lung function and pulmonary symptoms have been described in patients infected with helminths with a lung cycle. We have previously shown that infection with the nematode Strongyloides venezuelensis induced a significant increase in airway hyperreactivity in infected rats. The aim of the present study was to test the hypothesis that bronchodilation during the lung phase of parasite migration would favor completion of the life cycle and infection indices. For this purpose, S. venezuelensis infected rats were treated with salbutamol during the first 48 h after the nematode infection. At the dose used (0.25 mg/mL for 10 min every 4 h), treatment with salbutamol prevented changes in lung function during the parasite migration. This was accompanied by a significant increase in parasite burden, as assessed in the lung and the small intestine. Parasite infected and salbutamol-treated animals also showed a significant increase in concentration of IL-10 and IL-4 in homogenates of lungs during the worm migration that was followed by stronger lung eosinophilic inflammation at 5 dpi, after the larvae had left the host lung. Our data indicates that airway hyperactivity reduce parasite progression through the lung, facilitating the action of innate or adaptive immune mechanisms.

The effect of treatment with montelukast on in vitro interleukin‐10 production of mononuclear cells of children with asthma

The effects of leukotriene modifiers on IL-10 production have not been studied in children with asthma. The primary objective of this study was to determine the changes in IL-10 concentrations, clinical efficacy and peripheral blood eosinophil counts after treatment with montelukast. The study was conducted on 27 patients: 13 patients monoallergic to grass pollen during the pollen season (GPs group) and out of the pollen season (GPos group), and on 14 patients monoallergic to house dust mite (HDM) from May to September (HDM group). Main outcome measures were changes in concentrations of IL-10 in the supernatant after a 4-week treatment with montelukast. Measurements of asthma severity score, forced expiratory volume in 1 s (FEV1) and peripheral blood eosinophil counts were the secondary end-points. Montelukast resulted in a within-group significant increase in IL-10 concentration in the supernatant in the GPs (54.0 vs. 125.5 pg/mL) and in the HDM (51.2 vs. 77.1 pg/mL) group. Montelukast had no effect on changes of IL-10 concentration in the supernatant from peripheral blood mononuclear cell (PBMC) culture after non-sensitizing allergen stimulation. Montelukast significantly improved asthma control and FEV1, and significantly decreased eosinophil blood count in the GPs and in the HDM group after a 4-week treatment. Montelukast did not lead to changes of all measured parameters within the GPos group. Montelukast increased IL-10 concentration in supernatants from sensitizing allergen-stimulated PBMC culture obtained from children with asthma monoallergic to grass pollen during the pollen season, and from children with asthma monoallergic to HDM.

Antibiotic treatment in a murine model of sepsis: impact on cytokines and endotoxin release.

Experimental and clinical studies in sepsis indicate that antibiotic therapy may induce the release of endotoxin (LPS) from the outer membrane of gram-negative bacteria and therefore may affect the physiologic response and survival. The aim of this study was to evaluate if antibiotics commonly used to treat secondary peritonitis are capable of changing survival rates, proinflammatory and anti-inflammatory cytokine concentrations, and the release of endotoxin in a murine model of sepsis. Sepsis was induced by cecal ligation and puncture (CLP) in Swiss mice using an 18-gauge needle. The animals received injections of saline solution or imipenem or a combination of ciprofloxacin plus clindamycin every 8 h for 3 days. Antibiotic treatment induced an increase in survival rate and decreased plasma and peritoneal fluid levels of TNF-alpha and IL-6 at 6 and 24 h after CLP as compared with saline-treated animals. Antibiotic-treated animals also showed an early (6 h) decrease and a late (24 h) increase in IL-10 concentration in the peritoneal fluid. LPS concentrations were elevated in all groups, but imipenem-treated animals showed higher levels (2.2 EU/mL) than ciprofloxacin plus clindamycin (1.3 EU/mL) and saline-treated (1.5 EU/mL) groups. We conclude that antibiotic-induced endotoxin release is not a major determinant in the inflammatory response and prognosis in murine models of sepsis.

Hydrodynamically stable adhesion of endothelial cells onto a polypropylene hollow fiber membrane by modification with adhesive protein.

The effect on the adhesion of endothelial cells of immobilization of adhesion proteins onto a microporous polypropylene hollow fiber membrane for a conventional artificial lung was investigated with the aim of constructing a hybrid artificial lung bearing endothelial cells on the modified membrane. The membrane was modified by adsorption or covalent bonding of adhesion proteins of fibronectin, gelatin, or Pronectin. The density of adherent cells on the membrane modified by adsorption of or covalent bonding with fibronectin reached 1 x 10(5) cells/cm(2) after 1 day of incubation, which corresponds to the confluent cell density in a conventional culture dish, while the cell densities on the membranes modifieds with gelatin and Pronectin were 1-5 x 10(4) cells/cm(2) and 0.5-1 x 10(4) cells/cm(2), respectively. The loading of hydrodynamic shear force (0.23 N/m(2)) for 30 min to the membranes bearing endothelial cells had little effect on the density of adhered cells. The membrane covalently bonded with fibronectin could well maintain a high cell density even after the loading of a higher shear force of 1.15 N/m(2) for 180 min, however, at this level of shear force 49% of adhered cells on the fibronectin-adsorbed membrane were lost after 30 min. A partial cardiopulmonary bypass in rats employing the hybrid artificial lung model composed of a polypropylene hollow fiber membrane covalently bonded with fibronectin and endothelial cell adhesion showed the inhibition of tumor necrosis factor-Alpha release and an increase in IL-10 concentration in the circulating blood compared with that employing an artificial lung without cells. Long-term partial cardiopulmonary bypass employing the hybrid artificial lung model should be studied further.