14-hydroxydocosahexaenoate and Inflammation

Dexamethasone is an antiemetic that is frequently administered before or after the induction of anesthesia for prevention and treatment of perioperative nausea and vomiting. Dexamethasone has anti-inflammatory and immunosuppressive effects primarily via suppression of expression of inflammatory mediators. However, its effect on the eicosanoids and docosanoids that mediate the inflammatory response and inflammation resolution are unclear. We aimed to assess the effect of a single dose of intra-operative dexamethasone on peri‑operative eicosanoids involved in inflammation including leukotriene B. A subgroup of 80 patients from the randomised controlled PADDAG trial was enrolled into this substudy. They were allocated to receive 0, 4 or 8 mg dexamethasone administered intravenously at induction of anesthesia. Blood samples were collected before and 24 h after dexamethasone, for measurement of leukocytes, hs-CRP, LTB. Compared to the administration of placebo, neutrophil count was elevated (P<0.05) 24 h after administration of 4 and 8 mg dexamethasone. Dexamethasone (8 mg) resulted in increased levels of LTB. Antiemetic doses of dexamethasone given during surgery increased plasma LTB

Topics: Adult; Antiemetics; C-Reactive Protein; Dexamethasone; Docosahexaenoic Acids; Eicosanoids; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Female; Humans; Hydroxyeicosatetraenoic Acids; Inflammation; Leukocyte Count; Leukotriene B4; Lymphocyte Count; Male; Middle Aged; Neutrophils; Perioperative Care

White adipose tissue (WAT) is a complex organ with both metabolic and endocrine functions. Dysregulation of all of these functions of WAT, together with low-grade inflammation of the tissue in obese individuals, contributes to the development of insulin resistance and type 2 diabetes. n-3 polyunsaturated fatty acids (PUFAs) of marine origin play an important role in the resolution of inflammation and exert beneficial metabolic effects. Using experiments in mice and overweight/obese patients with type 2 diabetes, we elucidated the structures of novel members of fatty acid esters of hydroxy fatty acids-lipokines derived from docosahexaenoic acid (DHA) and linoleic acid, which were present in serum and WAT after n-3 PUFA supplementation. These compounds contained DHA esterified to 9- and 13-hydroxyoctadecadienoic acid (HLA) or 14-hydroxydocosahexaenoic acid (HDHA), termed 9-DHAHLA, 13-DHAHLA, and 14-DHAHDHA, and were synthesized by adipocytes at concentrations comparable to those of protectins and resolvins derived from DHA in WAT. 13-DHAHLA exerted anti-inflammatory and proresolving properties while reducing macrophage activation by lipopolysaccharides and enhancing the phagocytosis of zymosan particles. Our results document the existence of novel lipid mediators, which are involved in the beneficial anti-inflammatory effects attributed to n-3 PUFAs, in both mice and humans.

Topics: 3T3-L1 Cells; Adipocytes; Adipose Tissue, White; Animals; Anti-Inflammatory Agents; Cells, Cultured; Diabetes Mellitus, Type 2; Docosahexaenoic Acids; Esters; Fatty Acids, Unsaturated; Humans; Inflammation; Insulin Resistance; Linoleic Acid; Lipopolysaccharides; Macrophage Activation; Male; Mice; Mice, Inbred C57BL; Obesity; Phagocytosis