Toll-like receptor 4 stimulation before or after Streptococcus pneumoniae induced sepsis improves survival and is dependent on T-cells.

Introduction: Endotoxin tolerance improves outcomes from gram negative sepsis but the underlying mechanism is not known. We determined if endotoxin tolerance before or after pneumococcal sepsis improved survival and the role of lymphocytes in this protection.

Methods: Mice received lipopolysaccharide (LPS) or vehicle before or after a lethal dose of Streptococcus pneumoniae.

An A2A adenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models.

Background: The pathophysiology of sepsis is due in part to early systemic inflammation. Here we describe molecular and cellular responses, as well as survival, in A 2A adenosine receptor (AR) agonist treated and untreated animals during experimental sepsis.

Methods: Sepsis was induced in mice by intraperitoneal inoculation of live bacteria (Escherichia coli or Staphylococcus aureus) or lipopolysaccharide (LPS).

Eukaryotic translation initiation factor 5A small interference RNA-liposome complexes reduce inflammation and increase survival in murine models of severe sepsis and acute lung injury.

Background: Many novel therapeutics have failed to reduce all-cause mortality associated with severe sepsis. Eukaryotic translation initiation factor 5A (eIF5A) is a regulator of apoptosis as well as inflammatory cell activation, making it a potential target for sepsis therapy.

Methods: In a murine model of severe sepsis, mice were intraperitoneally challenged with lipopolysaccharide (LPS).

A new method for measuring blood-brain barrier permeability demonstrated with Europium-bound albumin during experimental lipopolysaccharide (LPS) induced meningitis in the rat.

The blood-brain barrier (BBB) is a critical extrameningeal site of injury during bacterial meningitis, manifested by enhanced BBB permeability (BBBP). Previous methods to measure altered BBBP during meningitis involve radioactive materials, or are poorly quantified. Europium (EU) is a fluorescent, non-radioactive metal that is a sensitive and stable marker.