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Letters in Drug Design & Discovery


ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Arachidonate Cascade in the Intensive Insulin Therapy for Critically Ill Patients with Sepsis: Roles of Prostaglandins on Hyperglycemia-Impaired Immunity

Author(s): Tatsurou Yagami, Yasuhiro Yamamoto, Hiromi Kohma and Kenkichi Takase

Volume 9, Issue 6, 2012

Page: [557 - 567] Pages: 11

DOI: 10.2174/157018012800673074

Price: $65


Intensive insulin therapy to control blood glucose level increases survival among critically ill patients in intensive care unit and hospital. Hyperglycemia is potentially harmful because it acts as a procoagulant, induces insulin resistance, causes apoptosis, impairs neutrophil function, increases the infection rate and is associated with the risk of morbidity and mortality. Hyperglycemia and insulin resistance are virtually universally in sepsis, which is the leading cause of death in critically ill patients. Initially, sepsis is characterized by a hyper-inflammatory response; but as sepsis persists, there is a shift toward an anti-inflammatory immunosuppressive state. The intensive insulin therapy also reduces the infection rate and the mortality in septic patients. Arachidonate cascade is one of the factors associated with hyperglycemia, sepsis and infection. The cascade is involved in the upregulation of proinflammtory cytokines and the dysfunction of immune cells. Especially, we focused on prostaglandin D2 (PGD2), which is produced from innate and adaptive immune cells. PGD2 is non-enzymatically metabolized to 15-deoxy-Δ12,14-PGJ2, (15d-PGJ2). 15d-PGJ2 is an endogenous ligand for the nuclear receptor, peroxysome proliferators-activated receptor γ (PPARγ) and induces apoptosis in the both immune cells. This review presents plausible roles of arachidonate cascade in hyperglycemia-impaired immunity. Furthermore, we shed light on therapeutic potentials of PPARγ ligands for critically ill patients under the insulin resistant state.

Keywords: Arachidonate cascade, 15-deoxy-Δ12, 14-prostaglandin J2, Intensive insulin therapy, Peroxysome proliferatorsactivated receptor γ, Insulin resistance, Thiazolidine

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