Galectin-3 aggravates experimental polymicrobial sepsis by impairing neutrophil recruitment to the infectious focus.

Sepsis is an overwhelming systemic inflammation resulting from an uncontrolled infection that causes extensive tissue damage, organ dysfunction and eventually death. A growing body of evidence indicates that impaired neutrophil migration to the site of infection is associated with poor outcome in sepsis. Here we show that galectin-3 (Gal-3), an endogenous glycan-binding protein, plays a critical role in sepsis outcome. We found that serum Gal-3 concentration increased in patients with septic shock and mice undergoing sepsis induced by cecal ligation and puncture (CLP). Mice deficient in Gal-3 (Gal-3 KO) are more resistant to sepsis induced by CLP, showing lower levels of biochemical markers and neutrophil infiltration for organ injury/dysfunction than those observed in wild-type mice (WT). Furthermore, Gal-3 KO mice show an increased number of neutrophils in the primary focus of infection and reduced bacterial loads in the peritoneal cavity, blood, and lungs. Mechanistically, blood neutrophils from septic mice show higher levels of surface-bound Gal-3 than neutrophils from naive mice. The deficiency of Gal-3 was associated with increased rolling and adhesion of these cells in mesenteric venules. Our results indicate that Gal-3, secreted during sepsis, inhibits neutrophil migration into the infectious focus, which promotes the bacterial spread and worsens the outcome of sepsis.

Chronic Toxoplasma gondii Infection Exacerbates Secondary Polymicrobial Sepsis.

Sepsis is a severe syndrome that arises when the host response to an insult is exacerbated, leading to organ failure and frequently to death. How a chronic infection that causes a prolonged Th1 expansion affects the course of sepsis is unknown. In this study, we showed that mice chronically infected with Toxoplasma gondii were more susceptible to sepsis induced by cecal ligation and puncture (CLP). Although T. gondii-infected mice exhibited efficient control of the bacterial burden, they showed increased mortality compared to the control groups. Mechanistically, chronic T. gondii infection induces the suppression of Th2 lymphocytes via Gata3-repressive methylation and simultaneously induces long-lived IFN-γ-producing CD4+ T lymphocytes, which promotes systemic inflammation that is harmful during CLP. Chronic T. gondii infection intensifies local and systemic Th1 cytokines as well as nitric oxide production, which reduces systolic and diastolic arterial blood pressures after sepsis induction, thus predisposing the host to septic shock. Blockade of IFN-γ prevented arterial hypotension and prolonged the host lifespan by reducing the cytokine storm. Interestingly, these data mirrored our observation in septic patients, in which sepsis severity was positively correlated to increased levels of IFN-γ in patients who were serologically positive for T. gondii. Collectively, these data demonstrated that chronic infection with T. gondii is a critical factor for sepsis severity that needs to be considered when designing strategies to prevent and control the outcome of this devastating disease.

IL-33 contributes to sepsis-induced long-term immunosuppression by expanding the regulatory T cell population.

Patients who survive sepsis can develop long-term immune dysfunction, with expansion of the regulatory T (Treg) cell population. However, how Treg cells proliferate in these patients is not clear. Here we show that IL-33 has a major function in the induction of this immunosuppression. Mice deficient in ST2 (IL-33R) develop attenuated immunosuppression in cases that survive sepsis, whereas treatment of naive wild-type mice with IL-33 induces immunosuppression. IL-33, released during tissue injury in sepsis, activates type 2 innate lymphoid cells, which promote polarization of M2 macrophages, thereby enhancing expansion of the Treg cell population via IL-10. Moreover, sepsis-surviving patients have more Treg cells, IL-33 and IL-10 in their peripheral blood. Our study suggests that targeting IL-33 may be an effective treatment for sepsis-induced immunosuppression.

Deficiência de ferro, prevalência de anemia e fatores associados em crianças de creches públicas do oeste do Paraná, Brasil / Iron deficiency and prevalence of anemia and associated factors in children attending public daycare centers in western Paraná, Brazil

OBJETIVO: Avaliar o estado nutricional de ferro, a prevalência de anemia e fatores associados, em crianças de 6 a 24 meses frequentadoras de creche pública em Cascavel, Região Oeste do Paraná, Brasil. MÉTODOS: O estudo transversal foi realizado com amostra aleatória de 256 crianças. A coleta de dados (questionário, medidas antropométricas e amostras de sangue) ocorreu de julho a setembro de 2007. A deficiência de ferro foi avaliada em termos de transferrina, hemoglobina, volume corpuscular médio, ferro sérico e eosinófilos. Na análise estatística dos dados foram obtidas as odds ratio bruta e ajustada (regressão logística), bem como os respectivos níveis de significância (p-valor). Para identificar diferenças significativas entre as medidas quantitativas, adotou-se a Análise de Variância e o teste de comparação múltipla de Tukey. RESULTADOS: A prevalência da anemia foi de 29,7 por cento, sendo que 77,3 por cento das amostras apresentaram baixa concentração de ferro. A antropometria não apontou deficiência de macronutrientes, porém mostrou obesidade acima dos índices médios. Os fatores associados à anemia e à deficiência de ferro foram: doenças frequentes na família (OR=10,02), condições de moradia (OR=5,05), tempo de creche (OR=3,05), número de moradores na residência (OR=2,83) e falta de saneamento (OR=2,20). CONCLUSÃO: A prevalência de anemia e a elevada deficiência de ferro detectada evidenciam um grave problema de saúde pública entre os pré-escolares do município de Cascavel, Paraná. Apesar da amplitude do problema, a anemia não está sendo reconhecida, prevenida e tratada adequadamente. Neste estudo são sugeridas algumas possíveis intervenções.

OBJECTIVE: This study assessed the iron levels and prevalence of anemia and associated factors in children aged 6 to 24 months attending public daycare centers in Cascavel, Western Paraná, Brazil. METHODS: This cross-sectional study included 256 randomly sampled children. Questionnaires were administered and anthropometric data and blood samples were collected from July to September 2007. Iron status was determined by measuring transferrin level, hemoglobin level, mean corpuscular volume, serum iron level and eosinophil count. Crude and adjusted (logistic regression) odds ratios and the respective significance levels (p-value) were obtained by statistical analysis. Analysis of variance and the Tukey's range test were used for identifying significant differences in the quantitative measurements. RESULTS: There was a 29.7 percent prevalence of anemia and 77.3 percent of the sample presented low iron levels. Anthropometry did not indicate macronutrient deficiencies but revealed above-average obesity rates. The factors associated with anemia and iron deficiency were family members constantly becoming sick (OR=10.02), poor living conditions (OR=5.05), time attending a daycare center (OR=3.05), number of individuals in the household (OR=2.83) and absence of sanitation (OR=2.20). CONCLUSION: The prevalence of anemia and the high iron deficiency rate evidenced a severe public health problem regarding the preschool children from Cascavel, Paraná. Despite the magnitude of the problem, anemia is not being detected, prevented and treated properly. This study suggests some possible interventions.