Abstract
Introduction: Oxygen therapy is a necessary component of the treatment provided to patients with acute respiratory failure. However, little is known about the impact of in vivo hyperoxia on pulmonary host defenses. Aim: Alveolar macrophages (AMs) constitute the first-line defense against inhaled pathogens. We investigated the effect of hyperoxia on Toll-like receptor (TLR)-mediated proinflammatory cytokine production by AMs. Methods: C57BL/6 mice were exposed to 80-90% oxygen for 96 h. AMs obtained from control mice and hyperoxia-exposed mice were stimulated ex vivo with the following: a TLR2 ligand, Pam3CSK4 (Pam3); a TLR4 ligand, lipopolysaccharide (LPS); a TLR5 ligand, flagellin (FLG); or a TLR3 ligand, poly I:C (PIC). Results: AMs from the hyperoxia-exposed mice produced significantly less TNF-α and IL-6 after Pam3, LPS, or FLG stimulation compared with AMs from the control mice. The decreased production of these cytokines was associated with reduced mRNA expression of the corresponding cytokines. Both cell surface and mRNA expression of TLR2, 4, and 5 in the AMs were significantly decreased following in vivo hyperoxia. In contrast, production of TNF-α after PIC stimulation did not differ between the two groups of AMs. Production of RANTES was decreased in AMs from hyperoxia-exposed mice after LPS, but not PIC, stimulation. No differences were observed in TLR3 mRNA expression in AMs between the control and hyperoxia-exposed mice. Conclusion: Hyperoxia impairs the reactivity of AMs to multiple TLR ligands typically associated with bacterial infection. This effect might result from a hyperoxia-induced decrease in TLR expression.
- © 2014 ERS
