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Inflammation in lung injury: the key mediators
S49 Is the development of acute lung injury influenced by increased levels of IL17 as a result of Treg/TH17 imbalance?
  1. R C A Dancer1,
  2. V D'Souza1,
  3. L Jeffery1,
  4. D Sansom1,
  5. C R Bassford1,
  6. G Perkins2,
  7. D R Thickett1
  1. 1University of Birmingham, Birmingham, UK
  2. 2University of Warwick, Warwick, UK

Abstract

Introduction Vitamin D is known to have profound effects on the immune system. We have shown that vitamin D is lower in patients with Acute Lung Injury (ALI) than in healthy or at risk controls and that in patients at risk of ALI post oesophagectomy, low vitamin D levels are associated with increased post-operative systemic inflammatory response and alveolar epithelial dysfunction. Studies have shown that when T cells are exposed to vitamin D, expression of IL17 decreases and regulatory capacity increases. We hypothesised that vitamin D deficiency may play a role in development of Acute Lung Injury (ALI) via changes in the balance between regulatory T cells (Treg) and pro-inflammatory Th17 cells.

Methods Plasma levels of 25-OH Vitamin D (Tandem mass spectrometry) and 1,25-OH Vitamin D (ELISA)were measured in samples from patients with ALI. Normal T cells were exposed to BAL from patients with ALI with or without addition of exogenous vitamin D and determined frequencies of Treg and Th17 cells using flow cytometry.

Results All samples tested had insufficient plasma levels of 25-OH vitamin D (<75 nmol/l, median 14.1 nmol/l). 1,25 vitamin D levels ranged from <20 to 176 pmol/l (reference range 43–144 pmol/l). 1,25 vitamin D levels were significantly related to both ITU survival (p=0.04) and survival at 90 days (p=0.04). Our initial findings suggest that BAL taken on day 0 of ARDS upregulated IL17 expression in normal T cells. This finding was blocked by exogenous 1,25-OH Vitamin D. By contrast, BAL taken on day 4 upregulated FoxP3 and CD25 expression, suggesting an increase in regulatory T cell activity.

Discussion These results suggest that in early ARDS an imbalance in T cells favouring expression of IL-17 may play a role in the inflammatory response to injury, and this may be attenuated by adequate vitamin D levels. Later in the course of the disease, Treg cells may predominate and play a role in resolution.

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