Targeting IL-16 to Protect Angiotensin II–induced Hypertension and Renal Injury

BACKGROUND: T cells are critical in the pathogenesis of hypertension. IL (interleukin)-16 is primarily produced and secreted by T cells; however, its role in hypertension remains unclear. METHODS: Serum samples from patients with hypertension were collected and analyzed using ELISA. A mouse model of Ang II (angiotensin II)–induced hypertension was established, and the role of IL-16 was investigated. RESULTS: IL-16 expression was elevated in patients with hypertension and positively correlated with both systolic and diastolic blood pressure. In Ang II–induced hypertensive mice, IL-16 expression was significantly upregulated in serum, kidney, and aortic tissues. IL-16–neutralizing antibody reduced both systolic and diastolic blood pressure in response to Ang II. Histological analyses revealed that renal injury and vascular remodeling were attenuated after IL-16 neutralization. Mechanistically, T-cell–derived IL-16 enhanced CD4 + (cluster of differentiation 4) T helper 1 cell function and mediated crosstalk with macrophages to stimulate inflammatory responses via activation of NF-κB (nuclear factor kappa B) and MAPK (mitogen-activated protein kinase) pathways. Conditioned medium from macrophages primed with IL-16–treated T helper 1 cells promoted smooth muscle cell proliferation and exacerbated endothelial cell damage during hypertension progression. CONCLUSIONS: Collectively, these findings indicate that T-cell–derived IL-16 exacerbates Ang II–induced hypertension and associated organ damage by promoting a T helper 1–macrophage–driven proinflammatory response.