Beneficial effects of antibacterial peptide PR-39 in a neonatal murine model of endotoxic shock.

The lethal effects occurring in neonatal (< 24-h old) BALB/c mice after challenge with E. coli lipopolysaccharide (LPS) were significantly counteracted by pretreatment with antibacterial peptide PR-39. Neonatal mice protection was probably related to the depressive effect of PR-39 on production of TNF-alpha known to be the major mediator of the lethal effects of neonatal endotoxic shock. Indeed, TNF-alpha plasmatic levels were consistently lower in pups pretreated with PR-39 compared with controls. Administration 24 h after challenge was no longer effective. Although PR-39 and anti-TNF-alpha doses were ineffective alone, when combined at different ratios protected neonatal mice. The present experiments show the potential use of peptide PR-39 in preventing neonatal endotoxic shock.