Antimicrobial Peptides and Systemic Inflammation: A Network Analysis.

INTRODUCTION

Antimicrobial peptides (AMPs) are essential components of the innate immune system, exhibiting diverse mechanisms of action.

OBJECTIVE

This study investigates the roles of cathelicidin (LL-37), alpha-defensins, and the S100 proteins S100A8 and S100A9 in systemic inflammation associated with sepsis, severe COVID-19, and acute pancreatitis using whole-blood bulk RNA-sequencing data.

RESULTS

Gene co-expression network analysis revealed that during septic shock and severe COVID-19, cathelicidin and alpha-defensins act synergistically in innate immune responses, while S100A8 and S100A9 function through distinct pathways related to mitochondrial metabolism and ubiquitin ligase binding. In contrast, the acute pancreatitis network displayed a different pattern, with CAMP co-expressed alongside S100A8 and S100A9, whereas alpha-defensins were downregulated and associated with inhibited mucosal immune responses.

CONCLUSION

These findings suggest that antimicrobial peptides contribute variably to systemic inflammation depending on the underlying insult, underscoring their complex, context-dependent roles in critical illness.