Effect of obesity in lung inflammation and remodeling in sepsis

• Grant number: 11/13040-5
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): October 01, 2011
• Effective date (End): September 30, 2012
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal researcher: Thais Martins de Lima Salgado
• Grantee: Thais Pineda Fungaro
• Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Sepsis is a disease with high incidence in the ICU, causing high costs to public and private health sectors. Despite the development of new antibiotics and improved intensive care measures, the mortality rate has not changed in the last two decades. Besides the known problems in treating this disease, currently there is as increasing incidence of obesity in the general population, including critically ill patients. Obese individuals are more susceptible to medical complications, including hypertension, type 2 diabetes, cardiovascular and pulmonary diseases. Studies have shown a higher incidence of lung disease in obese, due to changes in pulmonary mechanics and chronic systemic inflammation in these patients. The lung is one of the first organs affected in sepsis, and loss of function worsens the prognosis of patients with sepsis and may be related to the increase of mechanical ventilation and stay in the hospital observed in septic obese patients. Since the number of overweight and obese individuals tends to grow in the future, more research is needed to determine whether the inflammatory response and susceptibility of this population to respiratory tract infections are different from that with normal weight. Although some mechanisms involved in lung injury during sepsis are described, as high infiltration of neutrophils, cytokine production and collagen deposition, it is not clarified the role of obesity on pulmonary complications. For this reason we will study lung alterations after sepsis induction in normal and obese mice. We will use a model of diet-induced obesity to better mimic obesity developed by humans. We will evaluate pulmonary edema, production of adipokines and cytokines in plasma, lung and alveolar fluid and collagen deposition after 6 and 24 hours of LPS injection. We will also study the gene expression of proinflammatory mediators and enzymes related to tissue remodeling (MMP2 and MMP9) in the lung.