Endocrine Abstracts

Introduction: Vitamin D (VD) deficiency affects many autoimmune disorders requiring steroid therapy. In contrast to glucocorticoid immune suppressive doses for autoimmune diseases, patients with Addison’s disease (AD) require physiological replacement. There is growing evidence of a cross-talk between glucocorticoids (GC) and VD. However, VD’s interaction with the GC pathway remains poorly understood.

Methods: To explore this issue, CD14⁺ monocytes were obtained from 15 Addison patients and 30 healthy controls (HC). Cells were stimulated with VD and/or IL1β as an inflammatory stimulant for 24 h. To address inflammatory responses, gene expression levels of anti-inflammatory interleukin 10 (IL-10), programmed cell death ligand 1 (PD-L1) and VD receptor (VDR) were analyzed by qPCR and normalized to endogenous reference 18sRNA.

Results: The mRNA expression of IL1β-induced VDR was reduced after VD addition in AD patients and HC (AD_{IL1β/IL1β+VD} 343 vs 205, P=10⁻⁴; HC_{IL1β/IL1β+VD} 307 vs 213, P=2×10⁻⁴). IL-10 expression in AD patients showed a higher expression compared to HC in the culture conditions (untreated, IL1β, VD) and baseline CD14⁺ monocytes (Baseline P=0.05, untreated P=0.03, IL1β P=0.0007, VD P=0.007). No difference of IL-10 expression between HC and AD was observed in IL1β+VD culture condition (P=0.4). However, HC showed a strong activation of IL-10 expression after VD addition in IL1β-treated monocytes, whereas no activation of IL-10 could be observed after VD addition in IL1β-stimulated monocytes in AD patients (AD_{IL1β/IL1β+VD} 134 vs 126, P=0.7, HC_{IL1β/IL1β+VD} 76 vs 126, P=2×10⁻⁵). PD-L1 expression did not differ from HC, however, it increased after VD addition in IL1β-stimulated monocytes in HC, but only marginally in AD (AD_{IL1β/IL1β+VD} 12 vs 14, P=0.06, HC_{IL1β/IL1β+VD} 16 vs 23, P=0.006).

Conclusion: VD-induced downregulation of VDR implies a functional feedback mechanism of VDR, indicating a normal paracrine cellular regulation of VD in both AD patients and HC. Regarding anti-inflammatory parameters we showed an increased IL-10 expression in AD patients, which could be explained by their GC replacement therapy that may affect the immune response more than the endogenous cortisol of healthy individuals. Furthermore, the observation that anti-inflammatory cytokines IL-10 and PD-L1 do not respond to VD stimulation in AD patients may indicate a cross-inhibition of VD and GC potentially leading to an attenuation of the inflammatory response.