Anti-PAI-1 antibodies and Docking Site Peptide (DSP) enhance fibrinolysis up to eight-fold in rabbit empyema models.

The incidence of empyema continues to rise, with mortality rates reaching 20-27% in older, comorbid patients. Up to 30% of adults with empyema are unsuitable for surgery or conventional fibrinolytic therapy. Plasminogen activator inhibitor 1 (PAI-1) is a key inhibitor of fibrinolysis, promoting pleural fibrosis and lung restriction. Targeting PAI-1 could restore natural clot-dissolving mechanisms, offering a low-dose pharmacological intervention for this challenging condition and improving patient survival.

Researchers investigated anti-PAI-1 monoclonal antibodies (anti-PAI-1 mAbs) and a Docking Site Peptide (DSP) in rabbit models. Initially, these agents were tested in a chemically-induced pleural injury model. Subsequently, DSP was evaluated in a Streptococcus pneumoniae infectious empyema model. The study assessed the compounds' ability to modulate the PAI-1 mechanism and enhance the efficacy of exogenous fibrinolysins, specifically sctPA, in both early- and advanced-stage empyema.

Modulating different steps of the PAI-1 mechanism with anti-PAI-1 mAbs and DSP resulted in an up to eight-fold increase in the efficacy of exogenous fibrinolysins in the chemically-induced pleural injury model. This demonstrates a significant enhancement of fibrinolytic activity. The DSP was further tested in an infectious empyema model, showing robust improvements.

DSP increased the efficacy of sctPA by at least eight-fold in early-stage empyema and at least four-fold in advanced-stage empyema in the rabbit model. These findings strongly support the hypothesis that PAI-1 targeting can provide a novel, low-dose pharmacological treatment for empyema.