Sepsis: integrating basic research and clinical investigation

• Grant number: 06/58744-1
• Support Opportunities: Research Projects - Thematic Grants
• Start date: March 01, 2007
• End date: August 31, 2011
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Reinaldo Salomão
• Grantee: Reinaldo Salomão
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Pesquisadores principais: Eliezer Silva ; Ivan Hong Jun Koh

Abstract

Sepsis may be defined as a systemic repercussion of infection. Presenting as progressive stages - sepsis, severe sepsis and septic shock - from the same pathophysiological process, it is an emergency associated with increased morbidity and mortality. Clinical studies have demonstrated the increased incidence of sepsis and the dynamics of its epidemiology, regarding both the population it affects as well as its etiology. There has been progress in our understanding of sepsis pathophysiology, especially regarding bacterial recognition and induced cell activation. Interaction of clinical and experimental investigation is of paramount importance in sepsis research. There is a need of experimental studies to improve the understanding of pathophysiology and to develop therapeutic strategies, and of the clinical investigation that interfaces with basic research, using appropriate casuistic, representative of the spectrum of the disease, preferably multi-center, and laboratorial tools that allow to evaluate the complex inflammatory response seen in sepsis. These studies are important to define new therapeutic strategies and, importantly, patients among those with sepsis, which may benefit from these therapies. In this context, we planed our project in three related branches: -clinical and epidemiological investigation: to evaluate etiology, incidence, morbidity and mortality of sepsis in a multi-center study. This will provide important information that are needed due to the dynamic of epidemiology of sepsis and the scarce national data. We will focus on prognostic factors, from the host and the infecting microorganism, and on therapeutic interventions. This network will also be a source of biological specimens for the translational research studies. -clinical and experimental interface (translational research): the cellular adaptation across the continuum of sepsis syndrome will be evaluated, with focus on bacterial recognition and induced cellular activation. Functional data will be interpreted considering the clinical manifestations. -experimental investigation: In animal models of bacterial translocation and sepsis, we will evaluate the role of gut associated lymphoid tissues (GAL T) on immune activation in sepsis, focusing an the cellular subpopulations and the presence of inflammatory and anti-inflammatory mediators present in mesenteric lymph, and the effects on survival or death of the animals. The team involved in the project (coordinator, principal investigators, researchers, graduated and students), with the cooperation of researchers from Brazil and other countries, has the backgrounds needed to conduct this investigation, that in fact, represent the integration of their consolidated research experience. (AU)

Scientific publications

(8)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

S.C. SILVA; G.L. BAGGIO-ZAPPIA; M.K.C. BRUNIALTI; M.S.C. ASSUNÇAO; L.C.P. AZEVEDO; F.R. MACHADO; R. SALOMAO. Evaluation of Toll-like, chemokine, and integrin receptors on monocytes and neutrophils from peripheral blood of septic patients and their correlation with clinical outcomes. Brazilian Journal of Medical and Biological Research, v. 47, n. 5, p. 384-393, 2014-04-11. (06/58744-1)

MENDES, MARIALICE ERDELYI; BAGGIO-ZAPPIA, GIOVANA LOTICI; COLO BRUNIALTI, MILENA KARINA; FERNANDES, MARIA DA LUZ; RAPOZO, MARJORIE MARINI; SALOMAO, REINALDO. Differential expression of toll-like receptor signaling cascades in LPS-tolerant human peripheral blood mononuclear cells. Immunobiology, v. 216, n. 3, p. 285-295, MAR 2011. (06/58744-1)

FERNANDES, M. L.; MENDES, M. E.; BRUNIALTI, M. K. C.; SALOMAO, R.. Human monocytes tolerant to LPS retain the ability to phagocytose bacteria and generate reactive oxygen species. Brazilian Journal of Medical and Biological Research, v. 43, n. 9, p. 860-868, SEP 2010. (06/58744-1)

SEVERINO, PATRICIA; SILVA, ELIEZER; BAGGIO-ZAPPIA, GIOVANA LOTICI; COLO BRUNIALTI, MILENA KARINA; NUCCI, LAURA ALEJANDRA; RIGATO, JR., OTELO; COTRIM GUERREIRO DA SILVA, ISMAEL DALE; MACHADO, FLAVIA RIBEIRO; SALOMAO, REINALDO. Patterns of Gene Expression in Peripheral Blood Mononuclear Cells and Outcomes from Patients with Sepsis Secondary to Community Acquired Pneumonia. PLoS One, v. 9, n. 3, MAR 25 2014. (06/58744-1)

SEVERINO, PATRICIA; SILVA, ELIEZER; BAGGIO-ZAPPIA, GIOVANA LOTICI; COLO BRUNIALTI, MILENA KARINA; NUCCI, LAURA ALEJANDRA; RIGATO JUNIOR, OTELO; COTRIM GUERREIRO DA SILVA, ISMAEL DALE; MACHADO, FLAVIA RIBEIRO; SALOMAO, REINALDO. Gene expression profiling ofmononuclear cells frompatients with sepsis secondary to community-acquired pneumonia. GENOMICS DATA, v. 2, p. 3-pg., 2014-12-01. (06/58744-1)

GOMES, N. E.; BRUNIALTI, M. K. C.; MENDES, M. E.; FREUDENBERG, M.; GALANOS, C.; SALOMAO, R.. Lipopolysaccharide-induced expression of cell surface receptors and cell activation of neutrophils and monocytes in whole human blood. Brazilian Journal of Medical and Biological Research, v. 43, n. 9, p. 853-859, SEP 2010. (06/58744-1)

COLO BRUNIALTI, MILENA KARINA; SANTOS, MICHELLE CAROLINA; RIGATO, OTELO; MACHADO, FLAVIA RIBEIRO; SILVA, ELIEZER; SALOMAO, REINALDO. Increased Percentages of T Helper Cells Producing IL-17 and Monocytes Expressing Markers of Alternative Activation in Patients with Sepsis. PLoS One, v. 7, n. 5, p. e37393, 2012. (06/58744-1)

SALOMAO, REINALDO; COLO BRUNIALTI, MILENA KARINA; RAPOZO, MARJORIE MARINI; BAGGIO-ZAPPIA, GIOVANA LOTICI; GALANOS, CHRIS; FREUDENBERG, MARINA. BACTERIAL SENSING, CELL SIGNALING, AND MODULATION OF THE IMMUNE RESPONSE DURING SEPSIS. Shock, v. 38, n. 3, p. 227-242, 2012. (06/58744-1)