Submitted October 8, 2008
Accepted April 27, 2009
Treatment of invasive streptococcal infection with a peptide derived from human high molecular weight kininogen
Sonja Oehmcke*, Oonagh Shannon, Maren von Kockritz-Blickwede, Matthias Morgelin, Adam Linder, Anders I. Olin, Lars Bjorck, and Heiko Herwald
Department of Clinical Sciences, Division of Infection Medicine, Lund University, Lund, Sweden
Helmholtz Centre for Infection Research, Division of Infection and Immunology, Braunschweig, Germany
* Corresponding author; email: sonja.oehmcke{at}med.lu.se.
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 due to 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.
