Modulation of inflammatory and adrenergic pathways in hypertension: effects of β-blockers on cytokine release in Jurkat T cells

TL;DR

This study shows that certain beta-blockers, like carvedilol and nebivolol, protect immune cells under stress and reduce inflammation, while others like propranolol and metoprolol have limited effects.

Contribution

The study identifies differential protective and anti-inflammatory effects of third-generation β-blockers in oxidative-stressed T cells.

Findings

Carvedilol and nebivolol improved cell viability and reduced IL-6 and TNF-α under oxidative stress.

Propranolol and metoprolol showed limited protective effects in oxidatively stressed Jurkat cells.

Third-generation β-blockers may offer cardiovascular and immunomodulatory benefits.

Abstract

Research aimed to examine the effects of β-blockers on cytokine release in Jurkat cells under basal conditions and during oxidative stress. Oxidative stress was induced in Jurkat cells through the application of hydrogen peroxide (H2O2). Subsequently, β-blockers were administered to the incubation medium for 24 h, encompassing both intact and oxidatively stressed cell conditions. For β-blocker toxicity screening, the viability of Jurkat cells was determined using the MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) test. The IL-6, IL-17, and TNF-α content were measured in the supernatant of Jurkat cells incubated under different conditions. The study results show that propranolol, metoprolol, carvedilol, but not nebivolol, revealed toxic effects on the intact Jurkat cells (pc-p = 0.0001; pc-m > 0.0001; pc-c = 0.0003; pc-n = 0.0525). Under oxidative stress conditions, the viability of Jurkat cells decreased significantly (pc-H2O2 = 0.0001). Propranolol and metoprolol did not affect ((pc-p = 0.0001; pc-m > 0.0001), while nebivolol and carvedilol improved the viability of Jurkat cells incubated under oxidative stress conditions (pc-n = 0.002; pc-c = 0.0002). Oxidative stress significantly increased the cytokines (IL-6, TNF-α, IL-17) expression levels (pc-H2O2 < 0.0001; pc-H2O2 < 0.0001; pc-H2O2 < 0.0001) in Jurkat cells. Propranolol, carvedilol, nebivolol, and metoprolol did not significantly affect the expression levels of IL-6, TNF-α, and IL-17 in intact Jurkat cells, but decreased IL-6, TNF-α, and did not change IL-17 expression levels in Jurkat cells incubated under oxidative stress conditions. This study demonstrates that β-blockers can influence redox-sensitive cytokine pathways in Jurkat T lymphocytes when they are under oxidative stress. All the agents tested inhibited the production of IL-6 and TNF-α, but nebivolol and carvedilol showed the strongest protective and anti-inflammatory effects. These effects likely result from their combined properties, including antioxidant effects, nitric oxide modulation, and the regulation of NF-κB/MAPK pathways. In contrast, propranolol and metoprolol exhibited more limited activity. These findings suggest that third-generation β-blockers may offer both cardiovascular and immunomodulatory benefits, although further validation in primary immune cells and in vivo models is still required.

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