Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase

TLDR

The study aimed to determine whether inducible nitric oxide synthase (iNOS) protects the host from infectious agents and tumor cells while potentially causing tissue damage and shock. To test this, the authors generated iNOS‑deficient mice. iNOS‑knockout mice failed to control Listeria monocytogenes or lymphoma cells, were protected from LPS‑induced hypotension but still suffered liver damage and died at the same rate as wild type when primed, indicating both iNOS‑dependent and independent pathways to LPS‑induced shock.

Abstract

Mice deficient in inducible nitric oxide synthase (iNOS) were generated to test the idea that iNOS defends the host against infectious agents and tumor cells at the risk of contributing to tissue damage and shock. iNOS-/-mice failed to restrain the replication of Listeria monocytogenes in vivo or lymphoma cells in vitro. Bacterial endotoxic lipopolysaccharide (LPS) caused shock and death in anesthetized wild-type mice, but in iNOS-/-mice, the fall in central arterial blood pressure was markedly attenuated and early death averted. However, unanesthetized iNOS-/-mice suffered as much LPS-induced liver damage as wild type, and when primed with Propionobacterium acnes and challenged with LPS, they succumbed at the same rate as wild type. Thus, there exist both iNOS-dependent and iNOS-independent routes to LPS-induced hypotension and death.