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- Title
CNS Leptin Action Modulates Immune Response and Survival in Sepsis.
- Authors
Tschöp, Johannes; Nogueiras, Ruben; Haas-Lockie, Sarah; Kasten, Kevin R.; Castañeda, Tamara R.; Huber, Nadine; Guanciale, Kelsey; Perez-Tilve, Diego; Habegger, Kirk; Ottaway, Nickki; Woods, Stephen C.; Oldfield, Brian; Clarke, Iain; Chua Jr., Streamson; Sadaf Farooqi, I.; O'Rahilly, Stephen; Caldwell, Charles C.; Tschöp, Matthias H.
- Abstract
Sepsis describes a complex clinical syndrome that results from an infection, setting off a cascade of systemic inflammatory responses that can lead to multiple organ failure and death. Leptin is a 16 kDa adipokine that, among its multiple known effects, is involved in regulating immune function. Here we demonstrate that leptin deficiency in ob/ob mice leads to higher mortality and more severe organ damage in a standard model of sepsis in mice [cecal ligation and puncture (CLP)]. Moreover, systemic leptin replacement improved the immune response to CLP. Based on the molecular mechanisms of leptin regulation of energy metabolism and reproductive function, we hypothesized that leptin acts in the CNS to efficiently coordinate peripheral immune defense in sepsis. We now report that leptin signaling in the brain increases survival during sepsis in leptin-deficient as well as in wild-type mice and that endogenousCNSleptin action is required for an adequate systemic immune response. These findings reveal the existence of a relevant neuroendocrine control of systemic immune defense and suggest a possible therapeutic potential for leptin analogs in infectious disease.
- Subjects
SEPSIS; IMMUNE response; LIPOTROPIN; LEPTIN; ENERGY metabolism; CENTRAL nervous system
- Publication
Journal of Neuroscience, 2010, Vol 30, Issue 17, p6036
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.4875-09.2010