CD4(+) CD25(+) Foxp3(+) Regulatory T Cells, Dendritic Cells, and Circulating Cytokines in Uncomplicated Malaria: Do Different Parasite Species Elicit Similar Host Responses?

Clearing blood-stage malaria parasites without inducing major host pathology requires a finely tuned balance between pro- and anti-inflammatory responses. The interplay between regulatory T (Treg) cells and dendritic cells (DCs) is one of the key determinants of this balance. Although experimental models have revealed various patterns of Treg cell expansion, DC maturation, and cytokine production according to the infecting malaria parasite species, no studies have compared all of these parameters in human infections with Plasmodium falciparum and P. vivax in the same setting of endemicity. Here we show that during uncomplicated acute malaria, both species induced a significant expansion of CD4(+) CD25(+) Foxp3(+) Treg cells expressing the key immunomodulatory molecule CTLA-4 and a significant increase in the proportion of DCs that were plasmacytoid (CD123(+)), with a decrease in the myeloid/plasmacytoid DC ratio. These changes were proportional to parasite loads but correlated neither with the intensity of clinical symptoms nor with circulating cytokine levels. One-third of P. vivax-infected patients, but no P. falciparum-infected subjects, showed impaired maturation of circulating DCs, with low surface expression of CD86. Although vivax malaria patients overall had a less inflammatory cytokine response, with a higher interleukin-10 (IL-10)/tumor necrosis factor alpha (TNF-alpha) ratio, this finding did not translate to milder clinical manifestations than those of falciparum malaria patients. We discuss the potential implications of these findings for species-specific pathogenesis and longlasting protective immunity to malaria.

A comparative study of the efficiency of a pro-biotic and the anti-K99 and anti-A14 vaccines in the control of diarrhea in calves in Brazil.

A total of 99 pregnant cows were divided into eight groups submitted to the following treatments: group I (n = 29) consisted of unvaccinated cows whose calves did not receive a probiotic and was used as control. Group II (n = 10) consisted of vaccinated cows whose calves did not receive a probiotic. Groups III, IV and V (n = 10 neach) consisted of vaccinated cows whose calves received a probiotic for 5, 15 and 30 days, respectively. Groups VI, VII and VIII (n = 10 each) consisted of unvaccinated cows whose calves received a probiotic for 5, 15 and 30 days, respectively. Each animal in the vaccinated groups received two 5.0 ml vaccine doses containing pili K99 and A14 of Escherichia coli by the subcutaneous route. The probiotic containing Lactobacillus acidophilus at the dose of 2.0 x 10(8) live cells in 250 ml milk, was administered orally. All animals were observed clinically and bacteriologically and anti-K99 and anti-A14 antibody titers were determined in serum and colostrum. Mean calf weight was measured at birth and at 30 days of age. The results showed that a combination of the vaccine with the probiotic administered for 15 and 30 days was the most efficient treatment for the control of diarrhea.

The Gastroprotective Effect of Menthol: Involvement of Anti-Apoptotic, Antioxidant and Anti-Inflammatory Activities

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Changes in markers of muscle damage, inflammation and HSP70 after an Ironman triathlon race

We investigated the effects of an Ironman triathlon race on markers of muscle damage, inflammation and heat shock protein 70 (HSP70). Nine well-trained male triathletes (mean +/- SD age 34 +/- 5 years; VO(2peak) 66.4 ml kg(-1) min(-1)) participated in the 2004 Western Australia Ironman triathlon race (3.8 km swim, 180 km cycle, 42.2 km run). We assessed jump height, muscle strength and soreness, and collected venous blood samples 2 days before the race, within 30 min and 14-20 h after the race. Plasma samples were analysed for muscle proteins, acute phase proteins, cytokines, heat shock protein 70 (HSP70), and clinical biochemical variables related to dehydration, haemolysis, liver and renal functions. Muscular strength and jump height decreased significantly (P < 0.05) after the race, whereas muscle soreness and the plasma concentrations of muscle proteins increased. The cytokines interleukin (IL)-1 receptor antagonist, IL-6 and IL-10, and HSP70 increased markedly after the race, while IL-12p40 and granulocyte colony-stimulating factor (G-CSF) were also elevated. IL-4, IL-1beta and tumour necrosis factor-alpha did not change significantly, despite elevated C-reactive protein and serum amyloid protein A on the day after the race. Plasma creatinine, uric acid and total bilirubin concentrations and gamma-glutamyl transferase activity also changed after the race. In conclusion, despite evidence of muscle damage and an acute phase response after the race, the pro-inflammatory cytokine response was minimal and anti-inflammatory cytokines were induced. HSP70 is released into the circulation as a function of exercise duration.

Evidence of associations between cytokine gene polymorphisms and quality of life in patients with cancer and their family caregivers

PURPOSE/OBJECTIVES: To identify latent classes of individuals with distinct quality-of-life (QOL) trajectories, to evaluate for differences in demographic characteristics between the latent classes, and to evaluate for variations in pro- and anti-inflammatory cytokine genes between the latent classes. DESIGN: Descriptive, longitudinal study. SETTING: Two radiation therapy departments located in a comprehensive cancer center and a community-based oncology program in northern California. SAMPLE: 168 outpatients with prostate, breast, brain, or lung cancer and 85 of their family caregivers (FCs). METHODS: Growth mixture modeling (GMM) was employed to identify latent classes of individuals based on QOL scores measured prior to, during, and for four months following completion of radiation therapy. Single nucleotide polymorphisms (SNPs) and haplotypes in 16 candidate cytokine genes were tested between the latent classes. Logistic regression was used to evaluate the relationships among genotypic and phenotypic characteristics and QOL GMM group membership. MAIN RESEARCH VARIABLES: QOL latent class membership and variations in cytokine genes. FINDINGS: Two latent QOL classes were found: higher and lower. Patients and FCs who were younger, identified with an ethnic minority group, had poorer functional status, or had children living at home were more likely to belong to the lower QOL class. After controlling for significant covariates, between-group differences were found in SNPs in interleukin 1 receptor 2 (IL1R2) and nuclear factor kappa beta 2 (NFKB2). For IL1R2, carrying one or two doses of the rare C allele was associated with decreased odds of belonging to the lower QOL class. For NFKB2, carriers with two doses of the rare G allele were more likely to belong to the lower QOL class. CONCLUSIONS: Unique genetic markers in cytokine genes may partially explain interindividual variability in QOL. IMPLICATIONS FOR NURSING: Determination of high-risk characteristics and unique genetic markers would allow for earlier identification of patients with cancer and FCs at higher risk for poorer QOL. Knowledge of these risk factors could assist in the development of more targeted clinical or supportive care interventions for those identified.

Growth inhibitory, apoptotic and anti-inflammatory activities displayed by a novel modified triterpenoid, cyano enone of methyl boswellates

Triterpenoids are pentacyclic secondary metabolites present in many terrestrial plants. Natural triterpenoids have been reported to exhibit anti-inflammatory and anti-carcinogenic activities. Here, we show that modifications of ring A of boswellic acid (2 cyano, 3 enone) resulted in a highly active growth inhibitory, anti-inflammatory, pro-differentiative and anti-tumour triterpenoid compound called cyano enone of methyl boswellates (CEMB). This compound showed cytotoxic activity on a number of cancer cell lines with IC50 ranging from 0.2 to 0.6 mu M. CEMB inhibits DNA synthesis and induces apoptosis in A549 cell line at 0.25 mu M and 1 mu M concentrations, respectively. CEMB induces adipogenic differentiation in 3T3-L1 cells at a concentration of 0.1 mu M. Finally, administration of CEMB intra-tumourally significantly inhibited the growth of C6 glioma tumour xenograft in immuno-compromised mice. Collectively, these results suggest that CEMB is a very potent anti-tumour compound.

Evaluation of benzothiophene carboxamides as analgesics and anti-inflammatory agents

Nonsteroid anti-inflammatory drugs (NSAIDs) represent standard therapy for the alleviation of pain and inflammation. At present various classes of compounds have been reported as selective inhibitors of cyclooxygenase-2 (COX-2). However, they are associated with adverse side effects. To address these issues, we report here a new class of compounds that exhibit potent analgesic and anti-inflammatory response. Substituted bromo-benzothiophene carboxamides (4-11) were examined for their analgesic and anti-inflammatory properties. Our findings demonstrate that newly synthesized bromo-benzothiophene carboxamide derivatives 4, 6, and 8 attenuate nociception and inflammation at lower concentration than classical NSAIDs, such as ibuprofen. These compounds act by selectively inhibiting COX-2 and by disrupting the prostaglandin-E2-dependent positive feedback of COX-2 regulation, which was further substantiated by reduction in the levels of cytokines, chemokines, neutrophil accumulation, synthesis of prostaglandin-E2, expression of COX-2, and neutrophil activation at lower concentration than the classic NSAID ibuprofen. Toxicological study reveals that these compounds are well tolerated and metabolized to avoid any toxicity. Thus, these molecules represent a new class of analgesic and anti-inflammatory agents. (c) 2014 IUBMB Life, 66(3):201-211, 2014

The Mitogenic and Anti-Apoptotic Activity of Tumor Conditioned Medium on Endothelium

This study was designed to observe the effect of tumor conditioned medium (TCM) on the proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to TCM from breast carcinoma cell line MDA-MB-231, then we measured their proliferation, apoptosis and cell cycle distribution by MTT and flow cytometery (FCM). Following the stimulation of TCM, HUVECs showed higher pro-mitogenic and anti-apoptotic ability than did the negative control group (ECGF-free medium with 20% FBS), but a similar ability to the positive control group (medium with ECGF and 20% FBS). From these results, we can conclude that breast carcinoma cell line MDA-MB-231 could secret soluble pro-angiogenic factors that induce HUVEC angiogenic switching, including cell cycle progression, proliferation and growth. The role and character of these factors remain to be further studied.

Prognostic Role of Host Cyclooxygenase and Cytokine Genotypes in a Caucasian Cohort of Patients with Gastric Adenocarcinoma

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Neuroprotective and immunomodulatory properties of the new PPARγ agonist MDG548: an in vitro and in vivo study in PD models

Neuroinflammation is a key component of Parkinson’s disease (PD) neuropathology. Skewed microglia activation with pro-inflammatory prevailing over anti-inflammatory phenotypes may contribute to neurotoxicity via the production of cytokines and neurotoxic species. Therefore, microglia polarization has been proposed as a target for neuroprotection. The peroxisome proliferator-activated receptor gamma (PPARγ) is expressed in microglia and peripheral immune cells, where it is involved in macrophages polarization and in the control of inflammatory responses, by modulating gene transcription. Several studies have shown that PPARγ agonists are neuroprotective in experimental PD models in rodents and primates. however safety concerns have been raised about PPARγ agonists thiazolidinediones (TZD) currently available, prompting for the development of non-TZD compounds. Aim of this study was to characterize a novel PPARγ agonist non TZD, MDG548, for its potential neuroprotective effect in PD models and its immunomodulatory activity as the underlying mechanism of neuroprotection. The neuroprotective activity of MDG548 was assessed in vivo in the subacute MPTP model and in the chronic MPTP/probenecid (MPTPp) model of PD. MDG548 activity on microglia activation and phenotype was investigated in the substantia nigra pars compacta (SNc) via the evaluation of pro- (TNF-α and iNOS) and anti-inflammatory (CD206) molecules, with fluorescent immunohistochemistry. Moreover, cultured murine microglia MMGT12 were treated with MDG548 in association with the inflammagen LPS, pro- and anti-inflammatory molecules were measured in the medium by ELISA assay and phagocytosis was evaluated by fluorescent immunohistochemistry for CD68. MDG548 arrested dopaminergic cells degeneration in the SNc in both the subacute MPTP and the chronic MPTPp models of PD, and reverted MPTPp-induced motor impairment. Moreover, MDG548 reduced microglia activation, iNOS and TNF-α production, while induced CD206 in microglia. In cultured unstimulated microglia, LPS increased TNF-α production and CD68 expression, while decreased CD206 expression. MDG548 reverted LPS effect on TNF-α and CD206 restoring physiological levels, while strongly increased CD68 expression. Results suggest that the PPARγ agonist MDG548 is neuroprotective in experimental models of PD. MDG548 targets microglia polarization by correcting the imbalance between pro- over antiinflammatory molecules, offering a novel immunomodulatory approach to neuroprotection.

Spanish Sociology and Anti-Semitism Between passed prejudice and key to civilization

There is a significant lack of sociological research in Spain about anti-Semitism. At the same time there are alarming anti-Semitic tendencies and anti-Jewish stereotypes which are above the European average. This article aims to explain this lack of sociological research about anti-Semitism in Spain. Therefore two types of explications are offered: on the one hand side some structural problems will be shown which sociology in general had since its beginnings and which complicate the understanding of anti-Semitism. Furthermore explications regarding the specific social and historic situation in Spain and of Spanish sociology in particular will be exposed. It will be shown that for its rationalistic character and with the exception of very few authors – who are considered marginalized for practical research – sociology in general has had enormous problems in understanding anti-Semitism. The specific historic situation, Francoism, the dispute about the historic memory and the delayed institutionalisation of sociology could also explain the lack of sociological interest in the topic especially in Spain. The article shows that the study of anti-Semitism is not only relevant for struggling against this burden of society in many of its variants. Furthermore, thinking about anti-Semitism can help sociology to recognise its own epistemological problems. It can serve to criticise and improve instruments of sociological research by showing the limitations of the sociological approach and to uncover the importance of interdisciplinary research for understanding specific social phenomena. In that sense, anti-Semitism, far from being a marginal subject, can be considered a key topic in the process of civilisation and it can help us to decipher the contemporary Spanish society.

Studies on the exaggerated inflammatory response caused by streptococcus suis at systemic and central nervous system levels

Streptococcus suis de type 2 est un microorganisme pathogène d’importance chez le porc. Il est la cause de différentes pathologies ayant comme caractéristique commune la méningite. C’est également un agent émergeant de zoonose : des cas cliniques humains ont récemment été rapportés en Asie. Cependant, la pathogénèse de S. suis n’est pas encore complètement élucidée. Jusqu’à présent, la réponse pro-inflammatoire initiée par S. suis n’a été étudiée qu’in vitro. L’étude du choc septique et de la méningite requiert toujours des modèles expérimentaux appropriés. Au cours de cette étude, nous avons développé un modèle in vivo d’infection chez la souris qui utilise la voie d’inoculation intra-péritonéale. Ce modèle a servi à l’étude de la réponse pro-inflammatoire associée à ce pathogène, tant au niveau systémique qu’au niveau du système nerveux central (SNC). Il nous a également permis de déterminer si la sensibilité aux infections à S. suis pouvait être influencée par des prédispositions génétiques de l’hôte. Le modèle d’infection par S. suis a été mis au point sur des souris de lignée CD1. Les résultats ont démontré une bactériémie élevée pendant les trois jours suivant l’infection. Celle-ci était accompagnée d’une libération rapide et importante de différentes cytokines pro-inflammatoires (TNF-α, IL-6, IL-12p40/p70, IFN-ɣ) et de chémokines (KC, MCP-1 and RANTES), qui ont entraîné un choc septique et la mort de 20 % des animaux. Ensuite, pour confirmer le rôle de l’inflammation sur la mortalité et pour déterminer si les caractéristiques génétiques de l’hôte pouvaient influencer la réponse inflammatoire et l’issue de la maladie, le modèle d’infection a été étendu à deux lignées murines consanguines différentes considérées comme résistante : la lignée C57BL/6 (B6), et sensible : la lignée A/J. Les résultats ont démontré une importante différence de sensibilité entre les souris A/J et les souris B6, avec un taux de mortalité atteignant 100 % à 20 h post-infection (p.i.) pour la première lignée et de seulement 16 % à 36 h p.i. pour la seconde. La quantité de bactéries dans le sang et dans les organes internes était similaire pour les deux lignées. Donc, tout comme dans la lignée CD1, la bactériémie ne semblait pas être liée à la mort des souris. La différence entre les taux de mortalité a été attribuée à un choc septique non contrôlé chez les souris A/J infectées par S. suis. Les souris A/J présentaient des taux exceptionnellement élevés de TNF-α, IL-12p40/p70, IL-1β and IFN- γ, significativement supérieurs à ceux retrouvés dans la lignée B6. Par contre, les niveaux de chémokines étaient similaires entre les lignées, ce qui suggère que leur influence est limitée dans le développement du choc septique dû à S. suis. Les souris B6 avaient une production plus élevée d’IL-10, une cytokine anti-inflammatoire, ce qui suppose que la cascade cytokinaire pro-inflammatoire était mieux contrôlée, entraînant un meilleur taux de survie. Le rôle bénéfique potentiel de l’IL-10 chez les souris infectées par S. suis a été confirmé par deux approches : d’une part en bloquant chez les souris B6 le récepteur cellulaire à l’IL-10 (IL-10R) par un anticorps monoclonal anti-IL-10R de souris et d’autre part en complémentant les souris A/J avec de l’IL-10 de souris recombinante. Les souris B6 ayant reçu le anticorps monoclonal anti-IL-10R avant d’être infectées par S. suis ont développé des signes cliniques aigus similaires à ceux observés chez les souris A/J, avec une mortalité rapide et élevée et des taux de TNF-α plus élevés que les souris infectées non traitées. Chez les souris A/J infectées par S. suis, le traitement avec l’IL-10 de souris recombinante a significativement retardé l’apparition du choc septique. Ces résultats montrent que la survie au choc septique dû à S. suis implique un contrôle très précis des mécanismes pro- et anti-inflammatoires et que la réponse anti-inflammatoire doit être activée simultanément ou très rapidement après le début de la réponse pro-inflammatoire. Grâce à ces expériences, nous avons donc fait un premier pas dans l’identification de gènes associés à la résistance envers S. suis chez l’hôte. Une des réussites les plus importantes du modèle d’infection de la souris décrit dans ce projet est le fait que les souris CD1 ayant survécu à la septicémie présentaient dès 4 jours p.i. des signes cliniques neurologiques clairs et un syndrome vestibulaire relativement similaires à ceux observés lors de méningite à S. suis chez le porc et chez l’homme. L’analyse par hybridation in situ combinée à de l’immunohistochimie des cerveaux des souris CD1 infectées a montré que la réponse inflammatoire du SNC débutait avec une augmentation significative de la transcription du Toll-like receptor (TLR)2 et du CD14 dans les microvaisseaux cérébraux et dans les plexus choroïdes, ce qui suggère que S. suis pourrait se servir de ces structures comme portes d’entrée vers le cerveau. Aussi, le NF-κB (suivi par le système rapporteur de l’activation transcriptionnelle de IκBα), le TNF-α, l’IL-1β et le MCP-1 ont été activés, principalement dans des cellules identifiées comme de la microglie et dans une moindre mesure comme des astrocytes. Cette activation a également été observée dans différentes structures du cerveau, principalement le cortex cérébral, le corps calleux, l’hippocampe, les plexus choroïdes, le thalamus, l’hypothalamus et les méninges. Partout, cette réaction pro-inflammatoire était accompagnée de zones extensives d’inflammation et de nécrose, de démyélinisation sévère et de la présence d’antigènes de S. suis dans la microglie. Nous avons mené ensuite des études in vitro pour mieux comprendre l’interaction entre S. suis et la microglie. Pour cela, nous avons infecté des cellules microgliales de souris avec la souche sauvage virulente (WT) de S. suis, ainsi qu’avec deux mutants isogéniques, un pour la capsule (CPS) et un autre pour la production d’hémolysine (suilysine). Nos résultats ont montré que la capsule était un important mécanisme de résistance à la phagocytose pour S. suis et qu’elle modulait la réponse inflammatoire, en dissimulant les composants pro-inflammatoires de la paroi bactérienne. Par contre, l’absence d’hémolysine, qui est un facteur cytotoxique potentiel, n’a pas eu d’impact majeur sur l’interaction de S. suis avec la microglie. Ces études sur les cellules microgliales ont permis de confirmer les résultats obtenus précédemment in vivo. La souche WT a induit une régulation à la hausse du TLR2 ainsi que la production de plusieurs médiateurs pro-inflammatoires, dont le TNF-α et le MCP-1. S. suis a induit la translocation du NF-kB. Cet effet était plus rapide dans les cellules stimulées par le mutant déficient en CPS, ce qui suggère que les composants de la paroi cellulaire représentent de puissants inducteurs du NF-kB. De plus, la souche S. suis WT a stimulé l’expression de la phosphotyrosine, de la PKC et de différentes cascades liées à l’enzyme mitogen-activated protein kinase (MAPK). Cependant, les cellules microgliales infectées par le mutant déficient en CPS ont montré des profils de phosphorylation plus forts et plus soutenus que celles infectées par le WT. Finalement, la capsule a aussi modulé l’expression de l’oxyde nitrique synthétase inductible (iNOS) induite par S. suis et par la production subséquente d’oxyde nitrique par la microglie. Ceci pourrait être lié in vivo à la neurotoxicité et à la vasodilatation. Nous pensons que ces résultats contribueront à une meilleure compréhension des mécanismes sous-tendant l’induction de l’inflammation par S. suis, ce qui devrait permettre, d’établir éventuellement des stratégies plus efficaces de lutte contre la septicémie et la méningite. Enfin, nous pensons que ce modèle expérimental d’infection chez la souris pourra être utilisé dans l’étude de la pathogénèse d’autres bactéries ayant le SNC pour cible.

Inflammation and adipose tissue: effects of progressive load training in rats

Introduction: Cytokines (IL-6, IL-10 and TNF-alpha) are increased after exhaustive exercise in the rat retroperitoneal (RPAT) and mesenteric adipose tissue (MEAT) pads. On the other hand, these cytokines show decreased expression in these depots in response to a chronic exercise protocol. However, the effect of exercise with overload combined with a short recovery period on pro-and anti-inflammatory cytokine expression is unknown. In the present study, we investigated the regulation of cytokine production in the adipose tissue of rats after an overtraining-inducing exercise protocol. Methods: Male Wistar rats were divided into four groups: Control (C), Trained (Tr), Overtrained (OT) and recovered overtrained (R). Cytokines (IL-6, TNF-alpha and IL-10) levels and Toll Like Receptor 4 (TLR4), Nuclear Factor kBBp65 (NF-kBp65), Hormone Sensitive Lipase (HSL) and, Perilipin protein expression were assessed in the adipose tissue. Furthermore, we analysed plasma lipid profile, insulin, testosterone, corticosterone and endotoxin levels, and liver triacylglycerol, cytokine content, as well as apolipoprotein B (apoB) and TLR4 expression in the liver. Results: OT and R groups exhibited reduced performance accompanied by lower testosterone and increased corticosterone and endotoxin levels when compared with the control and trained groups. IL-6 and IL-10 protein levels were increased in the adipose tissue of the group allowed to recover, in comparison with all the other studied groups. TLR-4 and NF-kBp65 were increased in this same group when compared with both control and trained groups. The protein expression of HSL was increased and that of Perilipin, decreased in the adipose in R in relation to the control. In addition, we found increased liver and serum TAG, along with reduced apoB protein expression and IL-6 and IL-10 levels in the of R in relation to the control and trained groups. Conclusion: In conclusion, we have shown that increases in pro-inflammatory cytokines in the adipose tissue after an overtraining protocol may be mediated via TLR-4 and NF-kBp65 signalling, leading to an inflammatory state in this tissue.

Differential expression of cytokines, chemokines and chemokine receptors in patients with coronary artery disease

Monocytes/macrophages and lymphocytes have a key role in the pathogenesis of atherosclerosis through the production of inflammatory and anti-inflammatory cytokines. We evaluated mRNA expression and protein production of CCL2, CXCL8, CXCL9, CXCL10, IFN-gamma and IL-10 in vitro as well as the expression of the CCR2 and CXCR3 receptors in peripheral blood mononuclear cells (PBMCs) of patients with coronary artery disease (CAD) and healthy controls in the presence or absence of oxidized LDL (oxLDL). Patients with CAD showed higher constitutive expression of CCL2, CXCL8, CXCL9, CXCL10 and IFN-gamma mRNA and, after stimulation with oxLDL, higher expression of CCL2 and CXCL8 mRNA than the control group. We also detected higher levels of CCL2 and CXCL8 in supernatants of oxLDL-stimulated PBMCs from CAD patients than in corresponding supernatants from controls. Patients with CAD had a higher percentage of constitutive CCR2(+) and CXCR3(+) cells after stimulation with oxLDL. Among CAD patients, the main differences between the stable (SA) and unstable angina (UA) groups were lower IL-10 mRNA production in the latter group. Altogether, our data suggest that PBMCs from CAD patients are able to produce higher concentrations of chemokines and cytokines involved in the regulation of monocyte and lymphocyte migration and retention in atherosclerotic lesions. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Prevention of bacterial translocation using β-(1-3)-D-glucan in small bowel ischemia and reperfusion in rats

To investigate the role of β-(1-3)-D-glucan on 99mTc labelled Escherichia coli translocation and cytokines secretion in rats submitted to small bowel ischemia/reperfusion injury. Methods: Five groups (n=10 each) of Wistar rats were subjected to control(C), sham(S), group IR subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R), and group I/R+glucan subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R) and injected with 2mg/Kg intramuscular. Translocation of labelled bacteria to mesenteric lymph nodes, liver, spleen, lung and serum was determined using radioactivity/count and colony forming units/g(CFU/g). Serum TNFα, IL-1β, IL-6, IL-10 were measured by ELISA. Results: CFU/g and radioactivity/count were higher in I/R than in I/R+glucan rats. In C, S and S+glucan groups, bacteria and radioactivity/count were rarely detected. The I/R+glucan rats had enhancement of IL-10 and suppressed production of serum TNFα, IL-1β and, IL-6, compared to I/R untreated animals. Conclusion: The β-(1-3)-D-glucan modulated the production of pro-inflammatory and anti-inflammatory cytokines during bowel ischemia/reperfusion, and attenuated translocation of labelled bacteria