Multiple trauma induces serum production of host defence peptides

Lippross, Sebastian; Klueter, Tim; Steubesand, Nadine; Oestern, Stefanie; Mentlein, Rolf; Hildebrandt, Frank; Podschun, Rainer; Pufe, Thomas; Seekamp, Andreas; Varoga, Deike

doi:10.1016/j.injury.2011.03.044

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Volume 43, Issue 2 , Pages 137-142, February 2012

Multiple trauma induces serum production of host defence peptides☆

Sebastian Lippross
- Department of Trauma Surgery, University Medical Center of Schleswig-Holstein, Campus Kiel, Germany
- These authors contributed equally to the work.
Tim Klueter
- Department of Trauma Surgery, University Medical Center of Schleswig-Holstein, Campus Kiel, Germany
- These authors contributed equally to the work.
Nadine Steubesand
- Department of Trauma Surgery, University Medical Center of Schleswig-Holstein, Campus Kiel, Germany
Stefanie Oestern
- Department of Trauma Surgery, University Medical Center of Schleswig-Holstein, Campus Kiel, Germany
Rolf Mentlein
- Institute of Anatomy, Christian-Albrechts-University of Kiel, Germany
Frank Hildebrandt
- Department of Trauma, Hannover Medical School, Germany
Rainer Podschun
- Institute for Infection Medicine, University Hospital of Schleswig-Holstein, Campus Kiel, Germany
Thomas Pufe
- Department of Anatomy and Cell Biology, RWTH Aachen University, Aachen, Germany
Andreas Seekamp
- Department of Trauma Surgery, University Medical Center of Schleswig-Holstein, Campus Kiel, Germany
- These authors contributed equally to the work.
Deike Varoga
- Department of Trauma Surgery, University Medical Center of Schleswig-Holstein, Campus Kiel, Germany
- These authors contributed equally to the work.
- Corresponding author at: Department of Trauma Surgery, University of Kiel, A.-Heller Straße 7, 24105 Kiel, Germany. Tel.: +49 431 4581; fax: +49 431 5389.

Accepted 21 March 2011.

Abstract

Today multiple trauma still is associated with a high mortality. Although severe open fractures and wounds can give rise to local infections and sepsis, the overall infection rate of multiply injured patients is surprisingly low. We have investigated serum of multiply injured patients with respect to antibacterial properties and screened for host defence peptides (HDP) that constitute a class of fast acting and rapidly available molecules preventing bacterial infection.

Serum specimens were obtained from multiply injured patients. Radial diffusion assays were performed to investigate antimicrobial properties. Ultrafiltration and heat-inactivation were used to rule out antimicrobial activity of large proteins i.e. complement factors. ELISA was performed to analyse serum concentrations of the human beta-defensins 2 and 3 (hBD-2 and hBD-3), LL-37 and the proinflammatory cytokines interferon-gamma (IFN-γ) and interleukin-6 (IL-6).

Serum of multiply injured patients showed greater zones of inhibition in antimicrobial testing against Gram negative und positive bacteria. This effect was mediated by proteins smaller than 10kDa, inactivation of the complement system does not significantly reduce antibacterial action. hBD-2, hBD-3 and LL-37 concentrations were significantly elevated after trauma and followed different characteristic concentration curves. Similar patterns of concentration profiles were recorded for hBD-2/IL-6 and hBD-3/IFN-γ suggesting a stimulatory influence within their induction process.

With this study we provide evidence, that serum of multiply injured patients has by far higher antibacterial capacity than that of healthy donors. As possible mediators we have detected the HDP hBD-2, hBD-3 and LL-37 and their inducers in serum of multiply injured patients.

Keywords: Antimicrobial peptides, Polytrauma, Trauma surgery, Human beta-defensin, Cathelicidin