The relationship between pro-resorptive inflammatory cytokines and the effect of high dose vitamin D supplementation on their circulating concentrations.

Inflammatory/pro-resorptive cytokines and chemokines form part of a complex inter-dependent network and may be influenced by vitamin D. We investigated their inter-relationship and the effect of a loading dose of vitamin D. We measured plasma concentrations of an array of cytokines including tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), IL-6, IL-17, IL-8, granulocyte macrophage colony stimulating factor (GM-CSF), and the chemokine monocyte chemoattractant protein-1 (MCP-1). Cytokines, 25 (OH) vitamin D, 1,25 (OH)2 vitamin D, the Wnt inhibitor, DKK1 concentrations and bone turnover markers were measured at baseline and 3 months following a bolus dose (300,000 IU) of vitamin D2 in 39 subjects with vitamin D insufficiency. We observed strong correlations between TNF-α with GM-CSF (r=0.628, p<0.001), IL-17 (r=0.7, p<0.001) and MCP-1 (r=0.5, p=0.001), between IL-1ß with IL-17 (r=0.45, p=0.004) and between the 2 chemokines, IL-8 and MCP-1 (r=0.45, p=0.004). A positive correlation was seen between DKK1 and IL-1ß (r=0.35, p=-0.029). Following vitamin D loading at 3 months, the relationships between some of the cytokines changed (TNF-α and MCP-1: r=0.38, p=0.017, IL-1ß and IL-17: r=0.3, p=0.06). 1,25 (OH)2 vitamin D increased markedly following supplementation. Significant correlations were seen between 25 (OH) vitamin D (r=0.4 p=0.016) and 1,25 (OH)2 vitamin D (r=0.39 p=0.02) with plasma CTX (marker of bone resorption) at 3 months. TNF-α and IL-1ß increased significantly at 3 months (p<0.05). The close association between several cytokines is influenced by vitamin D status. Acute increases in 1,25 (OH)2 vitamin D, achieved with loading doses of vitamin D, lead to increases in pro-resorptive cytokines.