Inflammatory cytokines contribute to the pathogenesis of hypertension through effects on renal blood flow and sodium handling. This review will update recent advances that explore the renal actions of immune cells and cytokines in the pathogenesis of hypertension.
Populations of cells from both the innate and adaptive immune systems contribute to hypertension by modulating functions of the vasculature and epithelial cells in the kidney. Macrophages and T lymphocytes can directly regulate the hypertensive response and consequent target organ damage. Dendritic cells and B lymphocytes can alter blood pressure (BP) indirectly by facilitating T-cell activation. Proinflammatory cytokines, including tumor necrosis factor-α, interleukin 17, interleukin 1, and interferon-γ augment BP and/or renal injury when produced by T helper 1 cells, T helper 17 cells, and macrophages. In contrast, interleukin 10 improves vascular and renal functions in preclinical hypertension studies. The effects of transforming growth factor-β are complex because of its profibrotic and immunosuppressive functions that also depend on the localization and concentration of this pleiotropic cytokine.
Preclinical studies point to a key role for cytokines in hypertension via their actions in the kidney. Consistent with this notion, anti-inflammatory therapies can attenuate BP elevation in human patients with rheumatologic disease. Conversely, impaired natriuresis may further polarize both T lymphocytes and macrophages toward a proinflammatory state, in a pathogenic, feed-forward loop of immune activation and BP elevation. Understanding the precise renal actions of cytokines in hypertension will be necessary to inhibit cytokine-dependent hypertensive responses while preserving systemic immunity and tumor surveillance.
aDivision of Nephrology, Department of Medicine, Duke University and Durham VA Medical Centers, Durham, North Carolina, USA
bDivision of Nephrology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China
Correspondence to Steven D. Crowley, MD, Division of Nephrology, Department of Medicine, Duke University and Durham VA Medical Centers, Durham, NC 27710, USA. Tel: +919 684 9788; e-mail: email@example.com.