Immunomodulatory role of the spleen-liver axis: the influence of post-splenectomy time and LPS dose.

• Grant number: 23/15804-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2023
• End date: November 30, 2024
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alexandre Alarcon Steiner
• Grantee: Manoela Osorio Reis Sales
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/03418-0 - Hypothermia in Sepsis: causes and consequences, AP.TEM

Abstract

Previous results in our laboratory demonstrated a spleen-liver axis regulates TNF production in the bacterial lipopolysaccharide (LPS) induced systemic inflammation model in rats. Our proposal is that humoral signals released by spleen macrophages (which may include leukotriene B4) reach the liver via the bloodstream, where they interact with the liver's resident macrophages (Kupffer cells), which, due to their intravascular location, are well-positioned to respond to these signals. However, the results obtained to date involved a single dose of LPS and a single time post-splenectomy. Aiming to deepen the understanding of this immunoregulatory axis, we propose to investigate the influence of the LPS dose, as well as the post-splenectomy time. Male Wistar rats will undergo splenectomy 2, 7 and 21 days before LPS challenge. Control rats will undergo sham surgery. The LPS challenge will be carried out in one of 4 doses: 10, 100, 1,000 and 5,000 µg/kg. LPS will be administered via extension of a pre-implanted venous catheter, free from manipulation stress. TNF production will be quantified in liver and plasma samples collected 80 min after LPS injection.