Recombinant Interleukin‐19 Suppresses the Formation and Progression of Experimental Abdominal Aortic Aneurysms

Abstract

Background Interleukin‐19 is an immunosuppressive cytokine produced by immune and nonimmune cells, but its role in abdominal aortic aneurysm (AAA) pathogenesis is not known. This study aimed to investigate interleukin‐19 expression in, and influences on, the formation and progression of experimental AAAs. Methods and Results Human specimens were obtained at aneurysm repair surgery or from transplant donors. Experimental AAAs were created in 10‐ to 12‐week‐old male mice via intra‐aortic elastase infusion. Influence and potential mechanisms of interleukin‐19 treatment on AAAs were assessed via ultrasonography, histopathology, flow cytometry, and gene expression profiling. Immunohistochemistry revealed augmented interleukin‐19 expression in both human and experimental AAAs. In mice, interleukin‐19 treatment before AAA initiation via elastase infusion suppressed aneurysm formation and progression, with attenuation of medial elastin degradation, smooth‐muscle depletion, leukocyte infiltration, neoangiogenesis, and matrix metalloproteinase 2 and 9 expression. Initiation of interleukin‐19 treatment after AAA creation limited further aneurysmal degeneration. In additional experiments, interleukin‐19 treatment inhibited murine macrophage recruitment following intraperitoneal thioglycolate injection. In classically or alternatively activated macrophages in vitro, interleukin‐19 downregulated mRNA expression of inducible nitric oxide synthase, chemokine C‐C motif ligand 2, and metalloproteinases 2 and 9 without apparent effect on cytokine‐expressing helper or cytotoxic T‐cell differentiation, nor regulatory T cellularity, in the aneurysmal aorta or spleen of interleukin‐19–treated mice. Interleukin‐19 also suppressed AAAs created via angiotensin II infusion in hyperlipidemic mice. Conclusions Based on human evidence and experimental modeling observations, interleukin‐19 may influence the development and progression of AAAs.

Keywords

• abdominal aortic aneurysm
• angiogenesis
• cytokines
• interleukin‐19
• macrophages