The Leptin System: A Potential Target for Sepsis Induced Immune Suppression

Johannes      Tschop; Jonathan      R. Dattilo; Priya      S. Prakash; Kevin      R. Kasten; Matthias      H. Tschop; Charles      C. Caldwell

doi:10.2174/1871530311006040336

Abstract

Sepsis, which is defined as a systemic inflammatory response syndrome that occurs during infection, is associated with several clinical conditions and high mortality rates. As sepsis progresses immune paralysis can become severe, leaving an already vulnerable patient ill equipped to eradicate primary or secondary infections. At present the predominant treatments for sepsis have not demonstrated convincing efficacy of decreased mortality. During sepsis, it has been observed that leptin levels initially increase but subsequently decline. A body of evidence has demonstrated that central or systemic leptin can beneficially regulate immune function. In this report expression of leptin and its receptor, signaling, and function on leukocytes will be reviewed. Furthermore, the effects mediated by central and systemic leptin during sepsis will be reviewed. Altogether, the ability of leptin to beneficially enhance inflammation and the host response during sepsis supports its use as a therapeutic agent, particularly during the latter phases of the syndrome.

Keywords: T cell, macrophage, neutrophil, HPA, anti-microbial, Leptin, leptin protein receptor, G-CSF receptor, cytokine receptor homology, hematopoiesis, thermogenesis, choroid plexus, hypothalamus, ventromedial, Tyrosine Phosphorylation, extracellular signaling pathway, pro-opiomelanocortin, insulin receptor substrate, 3-phosphatidylinositol, 5-adenosine monophosphate, –, activated protein kinase, rapamycin, tumor necrosis factor alpha (TNF), cytokine signaling 3, Protein tyrosine phosphatase 1B, phosphatase 1B, peripheral blood mononuclear cells, autonomic nervous system, ANS, hypothalamo-pituitary adrenocortical, sympathetic nervous system, SNS