Complement in sepsis—when science meets clinics

FEBS Letters

article

Tom E. Mollnes¹  Markus Huber-Lang⁵ 

[1] Research Laboratory, Nordland Hospital Bodø;University of Tromsø;Department of Immunology, Oslo University Hospital, and University of Oslo;Centre of Molecular Inflammation Research, Norwegian University of Science and Technology;Institute for Clinical and Experimental Trauma-Immunology, University Hospital Ulm

关键词: C3a;    C5a;    complement activation;    sepsis;    therapy;    Toll-like receptors;   

DOI  :  10.1002/1873-3468.13881

来源: John Wiley & Sons Ltd.

【 摘 要 】

Sepsis as life-threatening organ dysfunction caused by microorganisms represents a dreadful challenge for the immune system. The role of the complement system as major column of innate immunity has been extensively studied in various sepsis models, but its translational value remains in the dark. Complement activation products, such as C3a and C5a, and their corresponding receptors provide useful diagnostic tools and promising targets to improve organ function and outcome. However, a monotherapeutic complement intervention irrespective of the current immune function seems insufficient to reverse the complex sepsis mechanisms. Indeed, sepsis-induced disturbances of cross talking complement, coagulation, and fibrinolytic cascades lead to systemic ‘thromboinflammation’, ultimately followed by multiple-organ failure. We propose to reliably monitor the complement function in the patient and to re-establish the immune balance by patient-tailored combined therapies, such as complement and Toll-like receptor inhibition. Our working hypothesis aims at blocking the ‘explosive’ innate immune recognition systems early on before downstream mediators are released and the inflammatory response becomes irreversible, a strategy that we name ‘upstream approach’.

【 授权许可】

Unknown