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Study of the production and action of antimicrobial peptides in mice submitted to LPS tolerance and sepsis by CLP

Grant number: 16/14109-2
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): October 01, 2016
Effective date (End): September 30, 2017
Field of knowledge:Health Sciences - Medicine
Principal researcher:Francisco Garcia Soriano
Grantee:Rubem Seitaro Gushi
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Mortality in severe sepsis and septic shock reach 46%, the treatment is restricted to antibiotics and organ support. There is no effective treatment to fit the immune system balance for adequate bacterial fighting. In this context, research to elucidate the molecular mechanisms behind sepsis acquire fundamental importance for the development of medicine. Sepsis can be understood as deregulation of systemic inflammatory response caused by an infection. Also called systemic inflammatory response syndrome (SIRS), which includes, besides sepsis, other responses to noninfectious etiologies, such as trauma and burn injuries. At a first moment this lack of control avoids reaching the resolution phase of acute inflammation, therefore, the perpetuation of neutrophil and macrophage actions cause tissue destruction. Afterward, sepsis progresses on to a state of immunosuppression, known as compensatory anti-inflammatory response syndrome (CARS). At this stage the tissue damage caused by the immune system stops, however the host's ability to suppress the widespread infection presents an impairment. In this context of elucidation and research of mechanisms that could open new therapeutic horizons for sepsis, in the mid-twentieth century a phenomenon known as LPS tolerance was discovered. It is characterized by reduced immune response against a new exposure to LPS in organisms previously exposed to low doses of this substance. Mice that were submitted to this process have lower mortality when exposed to real sepsis, reaching 40% of survival against 0% in control animals. Although many details have been discovered about the mechanisms behind this process, much remains unknown. In this context, many substances may be investigated. A class that has become more important recently are the AMPs (antimicrobial peptides). They are a large group of molecules (produced by cells such as neutrophils, macrophages and epithelial cells) known to provide protection against numerous pathogens in many organisms along the evolutionary scale. Recently, its importance enhanced in many human diseases related to autoimmunity and uncontrolled inflammatory response. The study of the role of these substances in sepsis is the focus of this project. (AU)