Intraperitoneal versus intranasal administration of lipopolysaccharide in causing sepsis severity in a murine model: a preliminary comparison

Abstract

<p>Community-acquired respiratory infection is the commonest cause of sepsis presenting to emergency departments. Yet current experimental animal models simulate peritoneal sepsis with intraperitoneal (<em>I.P.</em>) injection of lipopolysaccharide (LPS) as the predominant route. We aimed to compare the progression of organ injury between <em>I.P.</em> LPS and intranasal (<em>I.N.</em>) LPS in order to establish a better endotoxemia murine model of respiratory sepsis. Eight weeks old male BALB/c mice received LPS-<em>Escherichia coli</em> doses at 0.15, 1, 10, 20, 40 and 100 mg per kg body weight (e.g. LPS-10 is a dose of 10 mg/kg body weight). Disease severity was monitored by a modified Mouse Clinical Assessment Score for Sepsis (M-CASS; range 0–21). A M-CASS score ≥ 10 or a weight reduction of ≥ 20%, was used as a criterion for euthanasia. The primary outcome was the survival rate (either no death or no need for euthanasia). The progression of disease was specified as M-CASS, body weight, blood glucose, histopathological changes to lung, liver, spleen, kidney, brain and heart tissues. Survival rate in <em>I.P.</em> LPS-20 mice was 0% (2/3 died; 1/3 euthanized with M-CASS > 10) at 24 h. Survival rate in all doses of <em>I.N.</em> LPS was 100% (20/20; 3–4 per group) at 96 h. 24 h mean M-CASS post-<em>I.P.</em> LPS-10 was 6.4/21 significantly higher than <em>I.N.</em> LPS-10 of 1.7/21 (Unpaired t test, <em>P</em> < 0.05). Organ injury was present at 96 h in the <em>I.P.</em> LPS-10 group: lung (3/3; 100%), spleen (3/3; 100%) and liver (1/3; 33%). At 24 h in the <em>I.P.</em> LPS-20 group, kidney injury was observed in the euthanized mouse. At 96 h in the post-<em>I.N.</em> LPS-20 group, only lung injury was observed in 2/3 (67%) mice (Kruskal-Wallis test with Dunn’s, <em>P</em> < 0.01). At 24 h in the post-<em>I.N.</em> LPS-100 group all (4/4) mice had evidence of lung injury. Variable doses of <em>I.N.</em> LPS in mice produced lung injury but did not produce sepsis. Higher doses of <em>I.P.</em> LPS induced multi-organ injury but not respiratory sepsis. Lethal models of respiratory virus, e.g., influenza A, might provide alternative avenues that can be explored in future research.<br></p>