Lipopolysaccharide pre-conditioning is protective in lung ischemia-reperfusion injury

Background: The availability of suitable lung donors has remained a significant barrier to lung transplantation. The clinical relevance of an isolated positive Gram stain in potential donor lungs, which occurs in >80%, is unclear. Low doses of lipopolysaccharide (LPS) have been protective in several models of ischemia-reperfusion injury through a pre-conditioning response. We sought to demonstrate that low-dose LPS is protective against subsequent lung ischemia-reperfusion injury. Methods: Pathogen-free Long-Evans rats were pre-treated with vehicle or LPS 24 hours before 90 minutes of ischemia and up to 4 hours of reperfusion. Lungs were assessed for vascular permeability, myeloperoxidase content, bronchoalveolar lavage inflammatory cell and cytokine/chemokine content, as well as nuclear translocation of nuclear factor κB (NFκB) and activator protein-1 (AP-1), and interleukin-1 receptor-associated kinase-1 (IRAK-1) and stress-activated protein kinase (SAPK) activation. Results: Compared with positive controls, LPS pre-treatment resulted in reductions in vascular permeability (70%, p < 0.001), myeloperoxidase content (93%, p < 0.001), bronchoalveolar lavage inflammatory cells (91%, p < 0.001), and inflammatory cytokine/chemokine content (cytokine-induced neutrophil chemoattractant, 99%, p = 0.003; interleukin-1β, 72%, p < 0.0001; tumor necrosis factor-α, 76%, p < 0.0001), NFκB (86%, p < 0.001) and AP-1 (97%, p < 0.001) nuclear translocation, and IRAK-1 (87%, p < 0.001) and SAPK (80%, p < 0.001) phosphorylation. Conclusions: Lipopolysaccharide pre-treatment reduced lung injury and inflammatory mediator production after subsequent exposure to ischemia-reperfusion. Understanding the clinical significance of lipopolysaccharide in donor lungs has the potential to expand and clarify donor inclusion criteria.