Leptin Protects Against Mortality and Organ Dysfunction in A Two-Hit Trauma/Sepsis Model and is IL-6-Dependent. Issue 1 (July 2017)

• Record Type: Journal Article
• Authors: Negrin, Lukas Leopold; Jahn, Andreas; van Griensven, Martijn
• Is Part Of: Shock. Volume 48:Issue 1(2017)
• Publication Date: 2017-07
• Subjects: Adipokines -- immune system interaction -- leptin -- multiple hit -- sepsis -- trauma; Shock -- Periodicals; Shock -- Periodicals; Choc (Pathologie) -- Périodiques; Shock; Periodicals; 616.0475
• DOI: 10.1097/SHK.0000000000000837
• Languages: English
• ISSNs: 1073-2322

Abstract

ABSTRACT: Introduction: Leptin is thought to play an important role in the regulation of the immune system. In patients, leptin is inversely proportional to interleukin-6 (IL-6) levels. Thus, the objective of our study was to evaluate a dose-dependent therapeutic impact of leptin with possible IL-6-dependency on immune actions and outcome in a trauma/sepsis model. Materials and Methods: Sixty-nine wild-type and 63 IL-6 −/− mice were subdivided into three groups: trauma/sepsis group (first hit: femur fracture and hemorrhage; second hit: cecal ligation and puncture 2 days later), trauma group (first hit and laparotomy), sham group (laparotomy only). Each group received vehicle or leptin (2.5 μg/g (leptin1) or 5 μg/g (leptin2)) subcutaneously and was observed for 8 days after induction of the first hit. Mortality, humoral, and cellular immune markers were determined. Results: We revealed a dose-dependent anti-inflammatory effect of exogenous leptin in the sepsis groups and to some extent a pro-inflammatory effect in the sham groups. Leptin administration resulted in a decreased mortality in septic wild-type mice (trauma/sepsis vehicle group: 36.4%, trauma/sepsis leptin1 group: 25%, trauma/sepsis leptin2 group: 0%) and in an increased mortality in septic IL-6 −/− mice (53.8%, 83.4%, 100%). All mice of the trauma groups and sham groups survived. In wild-type trauma/sepsis mice, exogenous leptin led to increased levels of CD4 + and CD8 + in the spleen, and a less pronounced type IV hypersensitivity ( P ⩽ 0.039). Furthermore, it decreased the levels of tumor necrosis factor-α and IL-6, not reaching statistical significance. Conclusions: Due to the fact that leptin administration to traumatized and septic mice seems to have a positive effect on their outcome via IL-6 and does not negatively impact their medical condition if applied preventively, leptin might be a therapeutic agent for the prevention, or treatment of sepsis-related detrimental outcome after initial trauma. Abstract : Supplemental Digital Content is available in the text