An expanding body of evidence is rendering manifest that many cationic antimicrobial peptides are endowed with different properties and activities, well beyond their direct action on microbes. One of the most interesting and potentially important research avenue on the alternative use of antimicrobial peptides grounds on their affinity toward lipopolysaccharide (LPS), the endotoxin, responsible for the systemic inflammatory response syndrome (SIRS) and related, often fatal, disorders that can follow Gramnegative infections. Indeed, not only do several antimicrobial peptides, such as cathelicidins, display an ability to strongly bind LPS and break its aggregates, but they have also been demonstrated to suppress LPS-induced pro-inflammatory responses in vitro and to protect from sepsis in animal models. Although many aspects still need to be carefully evaluated – some of which are highlighted here – a mix of antimicrobial, LPS-sequestering/neutralization, and immunomodulatory features make cationic peptides, and especially synthetic or semi-synthetic amphiphilic compounds built on their scheme, attractive candidates for novel drugs to be administered in antisepsis therapies. These therapies will probably hinge either on compounds able to intervene at multiple points in the sepsis cascade or on the combination of two or more immunomodulators.
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