The relationship between pro-resorptive inflammatory cytokines and the effect of high dose vitamin D supplementation on their circulating concentrations.
Int Immunopharmacol. 2013 Sep 2. pii: S1567-5769(13)00331-7. doi: 10.1016/j.intimp.2013.08.010.
Karim Y, Turner C, Dalton N, Roplekar R, Sankaralingam A, Ewang M, Fogelman I, Hampson G.
Department of Immunology, St Thomas' Hospital, London SE1 7EH, UK.
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 3months following a bolus dose (300,000IU) 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-1β 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-1β (r=0.35, p=-0.029). Following vitamin D loading at 3months, the relationships between some of the cytokines changed (TNF-α and MCP-1: r=0.38, p=0.017, IL-1β 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 3months. TNF-α and IL-1β increased significantly at 3months (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.