The anti-inflammatory effects of Fuzapladib in an endotoxemic porcine model

Abstract

Endotoxemia is a systemic inflammatory condition caused by lipopolysaccharide (LPS) stimulation, which produces inflammatory cytokines. Fuzapladib (FZP) inhibits the activation of adhesion molecules found on the surface of inflammatory cells, mitigating inflammation. In this study, we evaluated the therapeutic effects of fuzapladib on inflammatory cytokines and cardio-respiratory function using an LPS-induced endotoxemic porcine model. Fifteen pigs were separated into three groups: low-FZP (n=5), high-FZP (n=5), and control (n=5). Pigs were administered LPS under general anesthesia, and complete blood cell count, blood biochemistry, inflammatory cytokines, and cardio-respiratory function were evaluated. Statistical analysis was performed using a linear mixed-effects model and the Steel-Dwass test, with a significance threshold of P<0.05. During the 4 hr experimental period, one pig in the control group and two pigs in the low-FZP group died due to hypoxemia and hypotension. In the early acute changes following LPS administration, the high-FZP group maintained significantly higher arterial oxygen partial pressure and normal blood pressure compared to the control group. Although interleukin-6 levels increased in all groups during the experiment, they were significantly lower in the high-FZP group compared to the control group. Other parameters showed no clinically significant differences. In conclusion, while high-dose fuzapladib did not reduce organ damage in the porcine endotoxemia model, it suppressed interleukin-6 production, delayed the progression of deterioration, and contributed to a reduction in mortality during the observation period.