Insulin-like growth factor-1/insulin-like growth factor-1 receptor signalling in macrophages facilitates recovery from acute lung injury.

Summary

In LPS-induced murine acute lung injury, intratracheal IGF-1 administered during the recovery phase reduced inflammatory cell counts and lung injury scores, whereas IGF-1R antagonism worsened them. IGF-1R was highly expressed on macrophages (notably CD11c+), and macrophage-focused IGF-1 signaling emerged as a pro-resolution pathway.

Key Findings

• Intratracheal recombinant IGF-1 given from day 4 post-LPS reduced inflammatory cells and lung injury scores.
• IGF-1R antagonism with JB1 during recovery increased inflammation and injury metrics.
• IGF-1R (CD221) was strongly expressed on macrophages, especially CD11c+ populations, implicating macrophage IGF-1 signaling in lung repair.

Clinical Implications

Suggests IGF-1/IGF-1R signaling as a therapeutic target to enhance resolution in ARDS; motivates biomarker and early-phase interventional studies focusing on timing, route, and macrophage-directed strategies.

Limitations

• Preclinical mouse model limits direct clinical generalizability
• Detailed sample sizes and off-target effects of JB1 are not described in the abstract

Future Directions

Validate IGF-1/IGF-1R macrophage signaling in human ARDS, define optimal dosing/timing/routes, and explore macrophage-targeted delivery or biomarkers to select responders.