D3.115 - Iloprost Attenuates Neutrophilic Airway Inflammation in a Murine Model of Type 2-Low Asthma

Neutrophilic asthma is a distinct phenotype of Type 2-low (T2-low) airway disease, characterized by corticosteroid resistance and severe clinical manifestations. Unlike eosinophilic asthma, the mechanisms underlying this neutrophil-predominant inflammation remain poorly understood, representing a significant unmet medical need. Prostacyclin (PGI₂) is a potent lipid mediator known to exert significant anti-inflammatory and vasodilatory effects by binding to its cognate prostacyclin receptor (IP receptor). Interestingly, data from the ImmGen database reveal that Ptgir (the gene encoding the IP receptor) mRNA is detectable in murine neutrophils, suggesting that these cells may be direct targets for PGI₂ signaling. Given its established clinical safety in treating pulmonary conditions, iloprost, a stable PGI₂ analogue, represents a promising lung-directed therapeutic approach to modulate neutrophilic inflammation. We aim to evaluate the efficacy of intranasal iloprost in modulating the neutrophilic inflammatory profile and immune cell recruitment in a murine asthma model.

A neutrophil-predominant airway inflammation model was established in female C57BL/6 mice via OVA/LPS sensitization and subsequent OVA aerosol challenge.  Iloprost (400 nM), a PGI₂ analog, or vehicle was administered intranasally before each challenge. The inflammatory cell composition in bronchoalveolar lavage fluid (BALF) was characterized by flow cytometry.

In the OVA/LPS-induced model, iloprost treatment significantly reduced total BALF cellularity by approximately 60%. Notably, iloprost markedly suppressed the accumulation of neutrophils, the hallmark of this T2-low model. Furthermore, while eosinophil and T-cell counts were significantly reduced, B-cell populations remained stable, suggesting that iloprost exerts a selective modulatory effect on specific inflammatory recruitment pathways rather than systemic immunosuppression.

Our findings demonstrate that iloprost effectively attenuates neutrophil-predominant airway inflammation. This highlights iloprost as a potential therapeutic candidate for patients with neutrophilic or T2-low asthma who are suboptimal responders to conventional therapies.