Olive Oil-Based Lipid Emulsion Ameliorates Immune Checkpoint Inhibitor-Induced Myocarditis via Inhibition of the...

The present study aimed to investigate the therapeutic efficacy and underlying mechanism of olive oil-based lipid emulsions (OOLE) in mitigating immune checkpoint inhibitor (ICI)-induced myocarditis triggered by ipilimumab (IPI) and nivolumab (NIVO). An in vitro model of inflammatory cardiomyocytes was established by co-culturing HL-1 cells with CD4⁺/CD8⁺ T cells isolated from ICI-treated mice. Cells were treated with 10% OOLE, followed by flow cytometry for apoptosis, ELISA for cytokine profiling (TNF-α, IL-1β, IL-6), and Western blot/qPCR for pathway analysis (NF-κB, NLRP3, IL-1β). In vivo, myocarditis was induced in mice via IPI/NIVO administration. Cardiac function was assessed using echocardiography, and inflammatory markers were evaluated in serum and myocardial tissue. The results showed that OOLE significantly reduced T cell-induced apoptosis and suppressed inflammatory cytokine production in HL-1 cells, while the expression of NF-κB, NLRP3, and IL-1β was downregulated. In vivo., OOLE improved left ventricular functional parameters and attenuated systemic inflammation. Molecular analyses confirmed that these protective effects were mediated via the inhibition of the NF-κB/NLRP3/IL-1β signaling axis. In conclusion, OOLE mitigates acute ICI-induced myocarditis by targeting the NF-κB/NLRP3/IL-1β pathway, demonstrating its potential in suppressing early inflammatory cascades and providing rapid cardioprotection. These findings highlight its promise as an adjunctive therapy for immune-related cardiac injury.