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Front Immunol. 2019 Mar 21;10:543. doi: 10.3389/fimmu.2019.00543. eCollection 2019.

Targeting Complement Pathways in Polytrauma- and Sepsis-Induced Multiple-Organ Dysfunction.

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Institute for Clinical and Experimental Trauma-Immunology, University Hospital of Ulm, Ulm, Germany.
Department of Immunology, Genetics and Pathology (IGP), Laboratory C5:3, Uppsala University, Uppsala, Sweden.
Institute for Systemic Inflammation Research (ISEF), University of Lübeck, Lübeck, Germany.
Division of Immunobiology, Cincinnati Children's Hospital, Cincinnati, OH, United States.
Department of Pathology & Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, United States.


Exposure to traumatic or infectious insults results in a rapid activation of the complement cascade as major fluid defense system of innate immunity. The complement system acts as a master alarm system during the molecular danger response after trauma and significantly contributes to the clearance of DAMPs and PAMPs. However, depending on the origin and extent of the damaged macro- and micro -milieu, the complement system can also be either excessively activated or inhibited. In both cases, this can lead to a maladaptive immune response and subsequent multiple cellular and organ dysfunction. The arsenal of complement-specific drugs offers promising strategies for various critical conditions after trauma, hemorrhagic shock, sepsis, and multiple organ failure. The imbalanced immune response needs to be detected in a rational and real-time manner before the translational therapeutic potential of these drugs can be fully utilized. Overall, the temporal-spatial complement response after tissue trauma and during sepsis remains somewhat enigmatic and demands a clinical triad: reliable tissue damage assessment, complement activation monitoring, and potent complement targeting to highly specific rebalance the fluid phase innate immune response.


MODS; clinical trial; complement activation; complement dysregulation; complement therapeutics; hemorrhagic shock; sepsis; trauma

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