Association of Vitamin D Status with Immune Markers in a Cohort of Healthy Adults

Abstract

Background

Immune function is affected by vitamin D status, but the optimal serum 25-hydroxy vitamin D [25(OH)D] concentration for immune function is not known.

Objectives

We hypothesized that 25(OH)D would be associated with markers of inflammation and immune activation.

Methods

We identified associations between 25(OH)D and immune markers from 361 healthy adults using polynomial regression. Linear regression was used to define the slope (β) of significant linear associations, and piecewise regression identified inflection points (IPs) for curvilinear associations with P < 0.05. IPs with a slope difference (SD) P < 0.05 before and after were significant.

Results

25(OH)D had linear, negative associations with interleukin (IL)-6 (β: −0.126; P = 0.009) and macrophage-derived chemokine (MDC) (β: −0.108; P = 0.04) and a linear, positive association with matrix metalloproteinase (MMP)-1 (β: 0.108; P = 0.04). Among the significant curvilinear associations, 2 showed negative associations below but positive associations above an IP with nearly significant SD P values, including percentage of effector-memory CD8 T cells (IP: 56.2 nmol/L; SD P = 0.067) and platelet concentration (IP: 38.9 nmol/L; SD P = 0.058). The opposite associations, positive below and negative above an IP, were seen for eotaxin (IP: 49.5 nmol/L; SD P = 0.049); interferon (IFN)-γ-induced protein-10 (IP-10) (IP: 71.8 nmol/L; SD P = 0.02); percentage of CD4 T cells expressing programmed cell death protein (PD)-1 (IP: 71.2 nmol/L; SD P = 0.01); percentage of Tregs expressing human leukocyte antigen, DR isotype (HLA-DR) (IP: 67.5 nmol/L; SD P < 0.0001); percentage of memory Tregs (IP: 68.8 nmol/L; SD P = 0.002); and percentage of memory Tregs expressing HLA-DR (IP: 68.8 nmol/L; SD P = 0.0008).

Conclusions

These findings are consistent with low vitamin D status allowing and higher vitamin D status dampening inflammation and immune activation. IP analysis identified possible thresholds for vitamin D effects on immune function. Two of 3 IPs at ∼50 nmol/L show higher inflammation below this concentration, suggesting 50 nmol/L as a minimum target for dampening inflammation. IPs at ∼70 nmol/L identify a threshold for CD4 T-cell activity, including Treg activation and IFN-γ-driven production of the T-cell chemokine IP-10, suggesting an optimal concentration for regulating adaptive immunity.

This study was registered at clinicaltrials.gov as NCT02367287.