IL-33 is overexpressed in the inflamed arteries of patients with giant cell arteritis

OBJECTIVE: To study the expression of interleukin (IL)-33 and to evaluate its relationship with macrophage polarisation in artery biopsy specimens from patients with giant cell arteritis (GCA). METHODS: IL-33, ST2, p-STAT-6 and perivascular IL-1 receptor-associated kinase 1 (p-IRAK1) tissue distribution was evaluated by immunohistochemistry. Inducible nitric oxide synthase and CD163 were also used by immunohistochemistry to evaluate the M1 and M2 polarisation, respectively. Quantitative gene expression analysis of IL-33, T-helper (Th)2-related transcription factor STAT6, Th2 cytokines (IL-4, IL-5, IL-25) and interferon (IFN)-γ was performed in artery biopsy samples obtained from 20 patients with GCA and 15 controls. Five additional patients who had received prednisone when the temporal artery biopsy was performed were also enrolled. RESULTS: IFN-γ and IL-33 were significantly overexpressed in the inflamed arteries of GCA patients. IL-33 overexpression was not accompanied by a concomitant increase of Th2 cytokines. Neovessels scattered through the inflammatory infiltrates were the main sites of IL-33 expression. The expression of IL-33 receptor ST2 and of p-IRAK1 was also increased in GCA patients. Arteries from glucocorticoid-treated patients had a lower expression of IL-33. IL-33 was accompanied by the expression of p-STAT6 and a clear M2 macrophages polarisation. CONCLUSIONS: A role for IL-33 in the inflammation of GCA patients is supported by these findings.