Tumor necrosis factor-α, kidney function, and hypertension

Hypertension is considered to be a lowgrade inflammatory condition characterized by the presence of various proinflammatory cytokines. Tumor necrosis factor alpha (TNF-alpha) is a constituent of the proinflammatory cytokines that is associated with salt-sensitive hypertension (SSH) and related renal injury. Elevated angiotensin II (ANG II) and other factors such as oxidative stress conditions promote TNF-alpha formation. Many recent studies have provided evidence that TNF-alpha exerts a direct renal action by regulating hemodynamic and excretory function in the kidney. The cytokine incites a strong natriuretic response and plays a part in regulation of the intrarenal renin-angiotensin system. The exact mechanistic role of TNF-alpha in the development of SSH is as yet poorly understood. While TNF-alpha antagonism has been shown to attenuate hypertensive responses in many hypertensive animal models, contrasting findings demonstrate that the direct systemic administration of TNF-alpha usually induces hypotensive as well as natriuretic responses, indicating a counterregulatory role of TNF-alpha in SSH. Differential activities of two cell surface receptors of TNF-alpha (receptor type 1 and type 2) may explain the contradictory functions of TNF-alpha in the setting of hypertension. This short review will evaluate ongoing research studies that investigate the action of TNF-alpha within the kidney and its role as an influential pathophysiological variable in the development of SSH and renal injury. This information may help to develop specific TNF-alpha receptor targeting as an effective treatment strategy in this clinical condition.