Treatment of invasive streptococcal infection with a peptide derived from human high-molecular weight kininogen.
Sepsis and septic shock remain an important medical problem, emphasizing the need to identify novel therapeutic opportunities. Hypovolemic hypotension, coagulation dysfunction, disturbed microcirculation, and multiorgan failure resulting from vascular leakage are often observed in these severe conditions. In the present study, we find that HKH20, a peptide derived from human high molecular weight kininogen (HK), down-regulates inflammatory reactions caused by Streptococcus pyogenes in a mouse model of sepsis. HK is a component of the pro-inflammatory and pro-coagulant contact system. Activation of the contact system in the bloodstream by S pyogenes leads to massive tissue damage in the lungs of the infected mice, which eventually results in the death of the animals. HKH20 inhibits activation of the contact system and protects mice with invasive S pyogenes infection from lung damage. In combination with clindamycin treatment, the peptide also significantly prolongs the survival of infected mice.
Department of Clinical Sciences, Division of Infection Medicine, Lund University, Lund, Sweden. Sonja.Oehmcke@med.lu.se
Sonja
S
Oehmcke
Oonagh
O
Shannon
Maren
M
von Köckritz-Blickwede
Matthias
M
Mörgelin
Adam
A
Linder
Anders I
AI
Olin
Lars
L
Björck
Heiko
H
Herwald
D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects; D005260:Female; D006801:Humans; D019679:Kininogen, High-Molecular-Weight / Q000627:therapeutic use*; D008171:Lung Diseases / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D010446:Peptide Fragments / Q000627:therapeutic use*; D013290:Streptococcal Infections / Q000188:drug therapy* / Q000473:pathology*; D013297:Streptococcus pyogenes / Q000187:drug effects; D015996:Survival Rate
D019679:Kininogen, High-Molecular-Weight; D010446:Peptide Fragments