Olive Oil-Based Lipid Emulsion (OOLE) ameliorates ICI-induced myocarditis by inhibiting the NF-κB/NLRP3/IL-1β pathway

Immune checkpoint inhibitors (ICIs), while revolutionary in cancer therapy, frequently induce immune-related adverse events (irAEs), with myocarditis being a rare but potentially fatal complication. This cardiotoxicity limits ICI utility and necessitates effective mitigation strategies. Current treatments often rely on broad immunosuppression, which can compromise anti-tumor efficacy and carry significant side effects. There's a critical need for targeted therapies that can specifically dampen the inflammatory cascade in the heart, such as the NF-κB and NLRP3 inflammasome pathways, to protect cardiac function without broadly suppressing the immune system.

Researchers investigated Olive Oil-Based Lipid Emulsion (OOLE) in both in vitro and in vivo models. For in vitro studies, inflammatory cardiomyocytes were simulated by co-culturing HL-1 cells with CD4⁺/CD8⁺ T cells isolated from ICI-treated mice. These cells were then treated with 10% OOLE. Key assays included flow cytometry for apoptosis, ELISA for cytokine profiling (TNF-α, IL-1β, IL-6), and Western blot/qPCR for pathway analysis of NF-κB, NLRP3, and IL-1β expression. In vivo, myocarditis was induced in mice through administration of ipilimumab (IPI) and nivolumab (NIVO). Cardiac function was evaluated via echocardiography, and inflammatory markers were assessed in serum and myocardial tissue.

OOLE treatment significantly reduced T cell-induced apoptosis in HL-1 cardiomyocytes. It also suppressed the production of key inflammatory cytokines, including TNF-α, IL-1β, and IL-6. Molecular analysis revealed that OOLE downregulated the expression of NF-κB, NLRP3, and IL-1β in these cells. > In vivo, OOLE improved left ventricular functional parameters and attenuated systemic inflammation in mice with ICI-induced myocarditis. Further molecular analyses confirmed that these protective effects were mediated through the inhibition of the NF-κB/NLRP3/IL-1β signaling axis. The study demonstrates OOLE's ability to dampen early inflammatory cascades and provide rapid cardioprotection.