Background/Purpose: Immunomodulatory effects of vitamin D were recently described in vitro, notably the expansion of regulatory T cells able to suppress inflammatory responses and the decrease of Th17 cells. However, studies of its effect in vivo in humans are lacking.

Objective : To explore the impact on inflammatory markers of a 6-month daily oral administration of vitamin D3 1000 IU versus no vitamin D, in aged patients with vitamin D insufficiency all receiving strontium ranelate.

Methods: A prospective, international phase III study with a 6-month double-blind period was performed to assess the efficacy and safety of a daily oral administration of strontium ranelate 2 g/vitamin D3 1000 IU fixed combination versus strontium ranelate 2 g alone. 150 patients (75 per group) included in this study were selected, after matching between the 2 groups for age, gender and baseline vitamin D level. Serum samples were collected at baseline and after 6 months of treatment. Quantitative analyses of 25 cytokines were performed using Luminex to study the impact of vitamin D daily oral administration on cytokine and chemokine profile. Statistical analysis was done using Wilcoxon matched pairs test (P value < 0.05 was considered significant).

Results: Sixty-nine women and 6 men were included in each treatment group, with a mean age 67.1 ± 7.0 years in the vitamin D group and 66.8 ± 8.3 years in the non-vitamin D group. Baseline vitamin D serum level was 44.9 ± 15.5 nmol/L in the vitamin D group and 44.6 ± 13.8 nmol/L in the non-vitamin D group.

Some cytokines/chemokines levels decreased over the 6-month follow-up only in the vitamin D group whereas they remained stable in the non-vitamin D group, i.e. IFN-α (40 at baseline vs. 34 pg/mL after 6 months of treatment, P=0.03), IL-1β (16 vs. 11 pg/mL, P=0.07), IL-15 (52 vs. 40 pg/mL, P=0.001), MIP-1α/CCL3 (44 vs. 39 pg/mL, P=0.008) and TNF-α (7.0 vs. 2.9 pg/mL, P<0.0001).

The only cytokine that varied significantly only in the non-vitamin D group and remained stable in the vitamin D group was IL-12 that increased over the 6-month follow-up (127 at baseline vs. 146 pg/mL after 6 months of treatment, P=0.002).

IL-1RA, IL-2R and MCP-1/CCL2 did not differ significantly between the 2 arms of treatment, and remain stable over the 6-month follow-up. GM-CSF, IL-4, IL-8/CXCL8, IP-10/CXCL10 and MIP-1β/CCL4 decreased while eotaxin increased in both groups.

Many other cytokines and chemokines levels remain below the sensitivity threshold of the test used, that preclude any conclusion regarding their evolution i.e. IFN-γ, IL-2, IL-5, IL-6, IL-7, IL-10, IL-13, IL-17, MIG/CXCL9 and RANTES.

Conclusion: In this study designed to assess the efficacy and safety of a daily oral administration of strontium ranelate/vitamin D3 combination versus strontium ranelate alone, a statistically significant decrease of pro-inflammatory cytokines and chemokines serum levels in patients receiving vitamin D was observed. Further studies are necessary to assess the clinical relevance of such vitamin D-induced pro-inflammatory cytokines/chemokines variations.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/evolution-of-the-cytokine-and-chemokine-profile-in-patients-receiving-oral-daily-vitamin-d-results-from-a-randomized-controlled-trial/