Lipopolysaccharide-Induced Lung Injury Is Independent of Serum Vitamin D Concentration

Lindy S Klaff,Gustavo Matute-Bello,Brent E Wisse,William A Altemeier,Sean E Gill,Peter Chen,Kristen Mittelsteadt,Christian Taube

doi:10.1371/journal.pone.0049076

Abstract

Vitamin D deficiency is increasing in incidence around the world. Vitamin D, a fat-soluble vitamin, has documented effects on the innate and adaptive immune system, including macrophage and T regulatory (Treg) cell function. Since Treg cells are important in acute lung injury resolution, we hypothesized that vitamin D deficiency increases the severity of injury and delays injury resolution in lipopolysaccharide (LPS) induced acute lung injury. Vitamin D deficient mice were generated, using C57BL/6 mice, through diet modification and limited exposure to ultraviolet light. At 8 weeks of age, vitamin D deficient and sufficient mice received 2.5 g/kg of LPS or saline intratracheal. At 1 day, 3 days and 10 days, mice were anesthetized and lung elastance measured. Mice were euthanized and bronchoalveolar lavage fluid, lungs and serum were collected. Ex vivo neutrophil chemotaxis was evaluated, using neutrophils from vitamin D sufficient and deficient mice exposed to the chemoattractants, KC/CXCL1 and C5a, and to bronchoalveolar lavage fluid from LPS-exposed mice. We found no difference in the degree of lung injury. Leukocytes were mildly decreased in the bronchoalveolar fluid of vitamin D deficient mice at 1 day. Ex-vivo, neutrophils from vitamin D deficient mice showed impaired chemotaxis to KC but not to C5a. Vitamin D deficiency modestly impairs neutrophil chemotaxis; however, it does not affect lung injury or its resolution in an LPS model of acute lung injury.

Highlights

Vitamin D deficiency is common in the United States (US) and worldwide, and serum levels in the US are lower than they were 10 years ago [1,2,3]
The effects of vitamin D on macrophage function have been well studied in Mycobacterium tuberculosis (MTb), and clinical tuberculosis is associated with vitamin D deficiency [17,18]
Alkaline phosphatase was significantly higher in the vitamin D deficient (VDD) group as compared with the vitamin D sufficient (VDS) group, likely reflecting increased bone resorption as a response to secondary hyperparathyroidism, resulting from vitamin D deficiency

Summary

Introduction

Vitamin D deficiency is common in the United States (US) and worldwide, and serum levels in the US are lower than they were 10 years ago [1,2,3]. The potential role of vitamin D on immune function has been explored in the last decade. Autoimmune diseases such as type 1 diabetes [10], multiple sclerosis [11] and asthma [12,13] have been associated with vitamin D deficiency. This is largely thought to be due to the effects of vitamin D on T-regulatory (Treg) cell function and vitamin D’s ability to stimulate Treg populations and enhance tolerance [14,15,16]. Neutrophils express the vitamin D receptor [21]; beyond the fact that patients with rickets have impaired neutrophil chemotaxis [22], little else is known about vitamin D regulation of neutrophil function

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Results

Conclusion