• Daniel Siegl, Thorsten Annecke, Bobby L Johnson, Christian Schlag, Andre Martignoni, Nadine Huber, Peter Conzen, Charles C Caldwell, and Johannes Tschöp.
• From the Department of Anaesthesiology, Ludwig Maximilian University of Munich, Munich, Germany (T.A., C.S., A.M., P.C., J.T.); Department of General and Visceral Surgery, University Hospital of Ulm, Ulm, Germany (N.H.); Division of Research, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio (B.L.J., C.C.C.); and Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians-University Munich, Munich, Germany (D.S.).
• Anesthesiology. 2014 Jul 1;121(1):98-114.

BackgroundObesity is a growing health problem and associated with immune dysfunction. Sepsis is defined as systemic inflammatory response syndrome that occurs during infection. Excessive inflammation combined with immune dysfunction can lead to multiorgan damage and death.MethodsThe authors investigated the influence of a class 1 obesity (body mass index between 30 and 34.9) on immune function and outcome in sepsis and the role of leptin on the immune response. The authors used a long-term high-fat-diet feeding model (12 weeks) on C57Bl/6 mice (n = 100) and controls on standard diet (n = 140) followed by a polymicrobial sepsis induced by cecal ligation and puncture.ResultsThe authors show that class 1 obesity is connected to significant higher serum leptin levels (data are mean ± SEM) (5.7 ± 1.2 vs. 2.7 ± 0.2 ng/ml; n = 5; P = 0.033) and improved innate immune response followed by significant better survival rate in sepsis (71.4%, n = 10 vs. 10%, n = 14; P < 0.0001). Additional sepsis-induced increases in leptin levels stabilize body temperature and are associated with a controlled immune response in a time-dependent and protective manner. Furthermore, leptin treatment of normal-weight septic mice with relative hypoleptinemia (n = 35) also significantly stabilizes body temperature, improves cellular immune response, and reduces proinflammatory cytokine response resulting in improved survival (30%; n = 10).ConclusionsRelative hyperleptinemia of class 1 obesity or induced by treatment is protective in sepsis. Leptin seems to play a regulatory role in the immune system in sepsis, and treatment of relative hypoleptinemia could offer a new way of an individual sepsis therapy.

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