Non-Selective Beta Blockers Reduce Inflammatory Bystander CD8+T Cell Activation in Decompensated Cirrhosis

Background & Aims: Liver cirrhosis is linked to immune dysfunction, involving both immunodeficiency and systemic inflammation. We have recently shown that bystander-activated CD8+T cells contribute to this inflammation. Non-selective beta blockers (NSBBs) are used in cirrhosis to lower portal pressure and reduce decompensation risk. However, evidence suggests that NSBBs have also anti-inflammatory effects.

Methods: Thus, we analyzed the impact of NSBBs on CD8+T cells in patients with decompensated cirrhosis (n=31). Ex vivo phenotypic and in vitro functional analyses of blood and ascites CD8+T cells were performed in matched patients on NSBB therapy (n=18) compared to those without (n=13).

Results: Ex vivo, CD8+T cells expressed adrenergic beta receptors (ABR1 and ABR2). In vitro, propranolol reduced the frequency of bystander-activated (CD69+CXCR6+) CD8+T cells and inhibited the production of pro-inflammatory cytokines upon IL12/15/18 stimulation, without affecting antigen-specific responses upon CMV peptide stimulation. Ex vivo phenotypic analysis confirmed the in vitro findings, showing reduced innate activation marker expression and lower frequencies of bystander-activated CD8+T cells in patients on NSBB therapy compared to those without. Notably, plasma and ascites NSBB levels from selected patients negatively correlated with bystander CD8+T cell frequencies.

Conclusions: Our study suggests that propranolol suppresses bystander-activated CD8+T cells in decompensated cirrhosis while maintaining antigen-specific functions, highlighting NSBBs as a potential strategy to mitigate systemic inflammation in cirrhosis.

Publication History

Article published online:
20 January 2025