Vasoactive intestinal peptide axis is dysfunctional in patients with Graves’ disease

Abstract

Vasoactive intestinal peptide (VIP) is a neuropeptide with potent immunoregulatory properties. Reduced serum VIP levels and alterations in VIP receptors/signaling on immune cells have been associated with diferent infammatory/autoimmune diseases. However, its role in autoimmune thyroid diseases (AITD) remains unknown. This study examined the interrelationship between VIP system, autoimmune background and thyroid hormones in peripheral immune cells in patients with AITD. Only Graves’ disease (GD) patients showed signifcantly lower serum VIP levels when compared to healthy subjects and to Hashimoto’s thyroiditis patients. Serum VIP levels were lower at the onset of GD, showing a signifcant negative correlation with thyroid hormone levels. The expression of VIP receptors, VPAC1 and VPAC2, was signifcantly upregulated in peripheral blood mononuclear cells (PBMC) from GD patients. There was an impairment of VIP signalling in these patients, probably attributable to a dysfunction of VPAC1 with preservation of VPAC2. The correlation between VPAC1 and thyroid hormone receptor expression in PBMC from healthy subjects was lost in GD patients. In summary, the VIP system is altered in peripheral immune cells of GD patients and this fnding is associated with diferent thyroid hormone receptor patterns, showing a dynamic inter-regulation and a prominent role of VIP in this setting.