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Evaluation of sepsis in low birth weight rats induced by intrauterine malnutrition

Grant number: 17/12604-9
Support type:Scholarships in Brazil - Master
Effective date (Start): October 01, 2017
Effective date (End): March 31, 2019
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Richardt Gama Landgraf
Grantee:Gabriela Araujo de Azevedo
Home Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

Undernourishment during pregnancy may affect fetal development and impair the maturation of the immune system, exerting prolonged negative effect on the immune response. Although these adaptations are beneficial in the short term, the permanent changes they cause can lead to adulthood diseases such as hypertension, glucose intolerance, insulin resistance, hyperlipidemia, hyperinsulinemia, obesity, chronic obstructive pulmonary disease, among others. In previous studies, it was shown that global intrauterine malnutrition caused hypocellularity in bone marrow and peripheral blood in Wistar rats. Furthermore, the reduction in the expression of adhesion molecules, elements in the extracellular matrix and in the generation of inflammatory mediators caused a reduction in the leukocyte migration in these animals. In this same model, we also observed reduction of the acute and allergic pulmonary inflammatory response, with lower production of cytokines and lipid mediators and high levels of circulating corticosterone. Together, these data could be related to the increased predisposition to infections presented by low birth weight individuals. Our group further demonstrated in Wistar rats that leukotrienes produced during allergic lung inflammation potentiate the ability of alveolar macrophages to phagocyte and kill Klebsiella pneumoniae via Fc³R. Nevertheless, little is known about infection control in low birth weight individuals. Sepsis is considered a syndrome of the systemic inflammatory response to infection, which causes death to millions of people worldwide, its pathophysiology is complex and involves the immune response, inflammatory mechanisms and the coagulation cascade, culminating in a state of intense alteration of homeostasis. The cellular, biochemical, and basic mechanisms of the inflammatory response occurring in sepsis in low birth weight animals are scarcely studied and understood.