Recombinant Antithrombin Alleviated Pulmonary Injury and Inflammation in LPS-Induced ARDS by Inhibiting IL17a/NF-κB Signaling.

Summary

Recombinant antithrombin reduced lung injury, permeability, inflammatory cytokines, immune infiltration, and NLRP3 activation in LPS-induced ARDS. rAT downregulated IL-17A and inhibited NF-κB; exogenous IL-17A blunted rAT efficacy, implicating the IL-17A/NF-κB axis as a key mechanism.

Key Findings

• rAT alleviated lung injury and reduced alveolar permeability in LPS-induced ARDS mice.
• rAT decreased serum inflammatory cytokines, immune cell infiltration, and NLRP3 inflammasome activation.
• rAT lowered Th17 proportions and IL-17A expression and inhibited NF-κB signaling in lung tissues.
• Exogenous IL-17A administration attenuated the protective effects of rAT, supporting IL-17A/NF-κB as the effector axis.

Clinical Implications

rAT may be repurposed for sepsis-induced ARDS to dampen IL-17A/NF-κB-driven inflammation; dosing, timing, and safety require clinical evaluation.

Limitations

• Single-species, single-injury model; human translational relevance remains to be demonstrated.
• No dosing optimization, pharmacokinetics, or safety/tolerability data presented.

Future Directions

Test rAT in pneumosepsis and ventilator-induced injury models; define dose–response and timing; and consider early-phase clinical trials targeting IL-17A/NF-κB signatures.