TY - JOUR
T1 - CNS leptin action modulates immune response and survival in sepsis
AU - Tschöp, Johannes
AU - Nogueiras, Ruben
AU - Haas-Lockie, Sarah
AU - Kasten, Kevin R.
AU - Castañeda, Tamara R.
AU - Huber, Nadine
AU - Guanciale, Kelsey
AU - Perez-Tilve, Diego
AU - Habegger, Kirk
AU - Ottaway, Nickki
AU - Woods, Stephen C.
AU - Oldfield, Brian
AU - Clarke, Iain
AU - Streamson, Chua
AU - Farooqi, I. Sadaf
AU - O'Rahilly, Stephen
AU - Caldwell, Charles C.
AU - Tschöp, Matthias H.
PY - 2010/4/28
Y1 - 2010/4/28
N2 - 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.Wenow report that leptin signaling in the brain increases survival during sepsis in leptin-deficient as well as in wild-type mice and that endogenous CNS leptin 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.
AB - 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.Wenow report that leptin signaling in the brain increases survival during sepsis in leptin-deficient as well as in wild-type mice and that endogenous CNS leptin 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.
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U2 - 10.1523/JNEUROSCI.4875-09.2010
DO - 10.1523/JNEUROSCI.4875-09.2010
M3 - Article
C2 - 20427662
AN - SCOPUS:77951663638
SN - 0270-6474
VL - 30
SP - 6036
EP - 6047
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 17
ER -