Alterations In Vitamin D Metabolism With Chronic Inflammation: Potential Implications In Inflammation-Induced Bone Loss

Abstract

Inflammatory conditions are often associated with compromised serum 25-(OH)D3 status and previous in vitro studies have shown that inflammatory cytokines may be involved. The objective of this study was to examine the effects of low dose LPS in vivo on inflammatory mediators and gene expression of VDR and hydroxylation enzymes involved in vitamin D metabolism. In experiment 1, 12-week-old male C57BL/6J mice (n=12/group) were randomly assigned to LPS (0, 0.01, and 0.1 mg/kg bw/d) delivered by slow release pellets over 30 and 90 days. In experiment 2, 16-week-old male C57BL/6J mice (n=10/group) were administered (i.p.) LPS (0, 0.1, 0.2 mg/kg bw/d) for 14 days. Body weight was not altered during either study. Low dose LPS increased hepatic TLR4, CD14, and IL-10 after 14 days. No alterations were observed in hepatic genes of interest after 30 days, but IL-10 and IL-1?; were decreased after 90 days. Splenic IL-1?; tended to increase (p = 0.05) after 14 days and IL-6 was increased in low dose LPS after 90 days. Hepatic CYP27A1 gene expression was decreased after 90 days, but not after 14 and 30 days. High dose LPS tended to decrease (p=0.08) splenic VDR after 14 days, and decreased CYP27B1 after 90 days. Renal CYP27B1 was decreased and CYP24A1 was increased after 14 days. A significant increased in plasma 25-(OH)D 3 was observed after 14 days, but not 30 days. Our data suggest that chronic low dose LPS has modest effects on VDR, decreases renal CYP27B1, and increases renal CYP24A1. Further studies should further explore how LPS alters renal gene expression of cytochrome P450 enzymes involved in vitamin D metabolism over time.