TY - JOUR T1 - The role of vitamin D in regulating the severity and duration of murine lung injury JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - 1816 AU - Sian Lax AU - Dhruv Parekh AU - Rachel Dancer AU - David Thickett Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/1816.abstract N2 - IntroductionVitamin D has been shown to modulate both innate and adaptive immune responses. Our research suggests patients with or at risk of developing acute lung injury (ALI) are severely vitamin D deficient/insufficient. As there are no licensed treatments for ALI we investigated the effect of vitamin D deficiency in a murine model of ALI to understand its mechanistic drivers.MethodsVitamin D deficiency in wild type (WT) mice was established using a vitamin D deficient diet. Combining this with intra-tracheal instillations of LPS (50µg) we analysed inflammation within the lungs of these mice compared to those fed on a vitamin D sufficient diet. In addition, systemic vitamin D supplementation was assessed by IP injection of cholecalciferol prior to LPS instillation.ResultsCompared to WT, vitamin D deficient mice had elevated lung damage at 24 and 48h post IT-LPS; increased Permeability Index (p=0.007, p=0.018) and RAGE expression (p=0.007, p=0.001). At 48h post IT-LPS vitamin D deficient mice had a build-up of apoptotic neutrophils (p=0.038), increased BALF granulocytes (p=0.042), elevated CXCL1/KC (p=0.012) and decreased oxygen saturation (p=0.016). Furthermore, pre-treatment of mice with normal vitamin D levels, with cholecalciferol reduced lung inflammation - fewer BALF granulocytes (7.6x105 to 4.3x105, p=0.135), and neutrophils (81% to 72%, p=0.068) 48h post IT-LPS (n=6).ConclusionOur data indicate that vitamin D deficiency significantly augments both the severity and duration of murine lung injury and exogenous vitamin D reduces lung responses to LPS even in mice with normal vitamin D levels. These data support the use of vitamin D to both prevent and potentially treat established ALI. ER -