Expression of interleukin‐32 in the inflamed arteries of patients with giant cell arteritis

Objective Giant cell (temporal) arteritis (GCA) is a vasculitis that mainly affects the large and medium arteries, especially the branches of the proximal aorta. Interleukin‐32 (IL‐32) is a recently described Th1 proinflammatory cytokine, and is mainly induced by interferon‐γ (IFNγ), IL‐1β, and tumor necrosis factor α (TNFα). This study was undertaken to investigate the expression and tissue distribution of IL‐32 in artery biopsy specimens from patients with GCA. Methods Quantitative gene expression analysis of IL‐32, IL‐1β, TNFα, IFNγ, IL‐6, and IL‐27 was performed in artery biopsy specimens obtained from 18 patients with GCA and 15 controls. Immunohistochemistry analysis was performed to evaluate IL‐32 tissue distribution and identify IL‐32–producing cells. Circulating Th1 lymphocytes were evaluated by flow cytometry. Results We demonstrated a strong and significant up‐regulation of IL‐32 at both the messenger RNA and protein levels in the artery biopsy samples from patients with GCA. IL‐32 was abundantly expressed by vascular smooth muscle cells of inflamed arteries and neovessels within inflammatory infiltrates. IL‐32 expression strongly correlated with the intensity of the systemic inflammatory response. IL‐32 overexpression was accompanied by strong overexpression of Th1 cytokines, such as IFNγ and IL‐27p28, in inflamed arteries from GCA patients. The Th1 lymphocyte population was also expanded among peripheral blood mononuclear cells from GCA patients and produced higher amounts of IL‐32 compared to controls. Conclusion Our findings indicate that overexpression of IL‐32 together with a clear Th1 response immunologically characterizes the inflammatory response in GCA. In particular, IL‐32 seems to be an important mediator of artery inflammation in GCA.