Interferon gamma in the pathogenesis of hypertension - recent insights

The mounting body of evidence underscores the pivotal role of interferon gamma (IFNγ) in the pathogenesis of hypertension, prompting exploration of the mechanisms by which this cytokine fosters a pro-inflammatory immune milieu, subsequently exacerbating hypertension. In this review, we delve into recent preclinical and clinical studies from the past two years to elucidate how IFNγ participates in the progression of hypertension.

IFNγ promotes renal CD8 + T cell accumulation by upregulating tubular PDL1 and MHC-I, intensifying cell-to-cell interaction. Intriguingly, a nucleotide polymorphism in LNK, predisposing towards hypertension, correlates with augmented T cell IFNγ production. Additionally, anti-IFNγ treatment exhibits protective effects against T cell-mediated inflammation during angiotensin II infusion or transverse aortic constriction. Moreover, knockout of the mineralocorticoid receptor in T cells protects against cardiac dysfunction induced by myocardial infarction, correlating with reduced IFNγ and IL-6, decreased macrophage recruitment, and attenuated fibrosis. Interestingly, increased IFNγ production correlates with elevated blood pressure, impacting individuals with type 2 diabetes, nondiabetics, and obese hypertensive patients.

These revelations spotlight IFNγ as the critical mediator bridging the initial phase of blood pressure elevation with the sustained and exacerbated pathology. Consequently, blocking IFNγ signaling emerges as a promising therapeutic target to improve the management of this 'silent killer.'