Vitamin D Binding Protein (DBP) Deficiency in Mice Decreases Systemic and Select Tissue Levels of Inflammatory Cytokines in a Murine Model of Acute Muscle Injury

Background Severe acute muscle injury results in massive cell damage, causing the release of actin into extracellular fluids where it complexes with the vitamin D binding protein (DBP). We hypothesized that a systemic Vitamin D deficiency would result in a less pro-inflammatory phenotype. Methods C57BL/6 wild-type and DBP deficient (DBP−/−) mice received intramuscular injections of either 50% glycerol or phosphate-buffered saline into thigh muscles. Muscle injury was assessed by histology. Cytokine levels were measured in plasma, muscle, kidney and lung. Results All animals survived the procedure but glycerol injection in both strains of mice showed lysis of skeletal myocytes, and inflammatory cell infiltrate. The muscle inflammatory cell infiltrate in DBP deficient mice had remarkably few neutrophils as compared to wild-type mice. The neutrophil chemoattractant CXCL1 was significantly reduced in muscle tissue from DBP−/− mice. However, there were no other significant differences in muscle cytokine levels. In contrast, plasma obtained 48 hours after glycerol injection revealed that DBP deficient mice had significantly lower levels of systemic cytokines IL-6, CCL2, CXCL1 and G-CSF. Lung tissue from DBP−/− mice showed significantly decreased amounts of CCL2 and CXCL1 as compared to glycerol-treated wild-type mice. Several chemokines in kidney homogenates following glycerol-induced injury were significantly reduced in DBP−/− mice: CCL2, CCL5, CXCL1 and CXCL2. Conclusion Acute muscle injury triggered a systemic pro-inflammatory response as noted by elevated plasma cytokine levels. However, mice with a systemic DBP deficiency demonstrated a change in their cytokine profile 48 hours after muscle injury to a less pro-inflammatory phenotype. Study Type Prognostic/Epidemiologic Level of Evidence Level III Correspondence: Randeep S. Jawa, MD, Department of Surgery, Stony Brook University Medical Center, Stony Brook, NY 11794-8191, tel: 631-444-8329, fax: 631-444-6176, randeep.jawa@stonybrookmedicine.edu Conflicts of Interest: None Funding: Stony Brook Department of Surgery competitive grant program (RSJ), and National Institutes of Health (RRK), Stony Brook University School of Medicine Office of Scientific Affairs Presentation: This work was presented in part at the 75th annual meeting of the American Association for the Surgery of Trauma in Waikoloa, HI in September, 2016. This work was presented with significant additional data at the 76th annual meeting of the American Association for the Surgery of Trauma in Baltimore, MD in September, 2017. © 2018 Lippincott Williams & Wilkins, Inc.

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