The role of the inflammatory reflex in the endotoxin tolerance

• Grant number: 18/14226-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2018
• End date: May 31, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Luiz Guilherme de Siqueira Branco
• Grantee: Brenda Kézia Lima Agostinho
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 16/17681-9 - Pathophysiological changes during systemic inflammation, AP.TEM

Abstract

Seventy years ago, the first study describing tolerance after bacteria inoculation in rabbits was published. Since that time, the importance of bacterial endotoxin tolerance has been researched in both humans and animals, protecting the organism from infectious agents. The spleen is an important modulator of systemic production of pro- and anti-inflammatory cytokines, producing pro-inflammatory cytokines first. However, after the activation of the sympathetic nervous system induced by inflammation and infection, cytokines production is attenuated, occurring an anti-inflammatory effect. The present study proposes that the anti-inflammatory effect of tolerance induced by repeated administration of lipopolysaccharide (LPS) depends of the inflammatory reflex through the spleen. LPS is an endotoxin present in the external membrane of Gram-negative bacteria. Splenectomy or fictional surgery will be performed in Wistar Hannover SPF rats (7-8 weeks) five days before LPS or vehicle administration. Animals will be separated in four groups (n=12), which will receive LPS (low dose, 100 µg/kg/mL) or vehicle (NaCl 0.9%, 1 mL/kg) (via intraperitoneal, ip). Core temperature will be measured each 5 minutes as an indicator of tolerance, by a datalogger implanted into the peritoneal cavity at the surgical procedure. Moreover, pro- and anti-inflammatory cytokines (TNF±, IL-1², IL-6, IFN³, IL-10) concentration will be measured to identify LPS-induced immune response. Therefore, the aim of the present study is to investigate the role of the inflammatory reflex in endotoxin tolerance.