Therapeutic Effects of TN13 Peptide on Acute Respiratory Distress Syndrome and Sepsis Models In Vivo

Background/Objectives: Regulation of acute inflammatory responses is crucial for host mortality and morbidity induced by pathogens. The pathogenesis of acute respiratory distress syndrome (ARDS) and sepsis are associated with systemic inflammation. p38 MAPK is a crucial regulator of inflammatory responses and is a potential target for acute inflammatory diseases, including ARDS and sepsis. We investigated the therapeutic effects of the TAT-TN13 peptide (TN13) on severe inflammatory diseases, including ARDS and sepsis, in vivo. Methods: To establish the ARDS model, C57BL/6 mice were intranasally (i.n.) administered lipopolysaccharide (LPS; 5 mg/kg, 40 mu L) to induce lung inflammation. As a positive control, dexamethasone (DEX; 0.2 mg/kg) was administered intraperitoneally (i.n.) 1 h post-LPS exposure. In the experimental groups, TN13 was administered intranasally (i.n.) at doses of 2.5 mg or 5 mg/kg at the same time point. In the LPS-induced sepsis model, mice received an intraperitoneal injection of LPS (20 mg/kg) to induce systemic inflammation. TN13 (25 mg/kg, i.p.) was administered 1 h after LPS treatment. Control mice received phosphate-buffered saline (PBS). Lung histopathology, inflammatory cell infiltration, cytokine levels, and survival rates were assessed to evaluate TN13 efficacy. Results: TN13 significantly reduced inflammatory cell recruitment and cytokine production in the lungs, thereby mitigating LPS-induced ARDS. In the sepsis model, TN13 treatment improved survival rates by suppressing inflammatory responses. Mechanistically, TN13 exerted its effects by inhibiting the p38 MAPK/NF-kappa B signaling pathway. Conclusions: These results collectively suggested that TN13 could be an effective treatment option for severe inflammatory diseases.