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Contact system activation in severe infectious diseases

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Abstract

Hemostasis is a sensitive and tightly regulated process, involving vascular endothelium and blood cells, as well as factors of the coagulation and fibrinolytic cascades. In severe and invasive infectious diseases, the equilibrium between the procoagulant and anticoagulant status of the host may change dramatically and can induce life-threatening complications. A growing body of evidence suggests that the contact system, also known as the intrinsic pathway of coagulation or kallikrein/kinin system, participate in these processes. Contact activation leads to the release of the highly potent proinflammatory peptide bradykinin and initiates the intrinsic pathway of coagulation. Several studies have shown a systemic activation of the contact system in animal models of severe bacterial infections, and similar findings were also reported when monitoring patients suffering from sepsis, severe sepsis, or septic shock. Complications resulting from a systemic activation of the contact system are pathologically high levels of bradykinin, consumption of contact factors, and a subsequent induction of inflammatory reactions. These conditions may contribute to serious complications such as hypotension and vascular leakage. Here, we summarize the state of the art in this field of research with a focus on the contact system, and we also discuss a potential role for the contact system as a target for the development of novel antimicrobial strategies.

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Acknowledgments

This work was supported in part by the foundations of Alfred Österlund, Crafoord, Greta and Johan Kock, the Blood and Defence Network and the Vascular Wall Programme at Lund University, the Medical Faculty, Lund University, the Swedish Research Council, and Hansa Medical. Hansa Medical that in part funded this study has filed patent applications on HKH20. SO and HH are listed as inventors and the applications are pending.

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  1. Department of Clinical Sciences, Division of Infection Medicine, BMC, B14, Lund University, Tornavägen 10, SE-221 84, Lund, Sweden

    Sonja Oehmcke & Heiko Herwald

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  1. Sonja Oehmcke
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  2. Heiko Herwald
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Correspondence to Sonja Oehmcke.

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Oehmcke, S., Herwald, H. Contact system activation in severe infectious diseases. J Mol Med 88, 121–126 (2010). https://doi.org/10.1007/s00109-009-0564-y

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