Role of H2 histamine receptors in intestinal epithelial barrier dysfunction induced by sepsis

• Grant number: 22/15013-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2023
• End date: January 31, 2024
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Rafael Simone Saia
• Grantee: Marcos Vinícius Aguilar
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Sepsis is characterized by organ dysfunction as a consequence of exacerbated inflammatory response against infection. In its acute phase, it is not only associated with a high concentration of pro-inflammatory cytokines, but also with feedback and perpetuation of the response due to tissue damage caused by this process. Among the infected organs is the intestine, which, due to the extension of its surface and because its lumen is a niche of a dense microbial population, can generate deleterious systemic consequences. Physiologically, a series of controls prevent the excessive influx of bacteria to the lamina propria, such as the secretion of mucus and antimicrobial factors and the presence of junctions that unite the adjacent epithelial cells of the mucosa and seal off the paracellular pathway. However, in sepsis, the exacerbated inflammatory response damages the barrier, which increases its permeability to luminal antigens and, due to its systemic diffusion, amplifies the inflammatory response and organ dysfunction. Histamine, a mediator produced and elicited by mast cells, undergoes increased concentration in pathophysiological contexts. Histamine is correlated with the severity of the disease, the inflammatory stimulus and organic dysfunction, justifying the study of this mediator in the dysfunction of the intestinal epithelial barrier. The present study will evaluate the participation of histamine H2 receptors in the modulation of the inflammatory response (systemic and in the intestinal mucosa), intestinal hyperpermeability and bacterial translocation in an experimental model of polymicrobial sepsis.