OBJECTIVE: Diabetic patients have elevated blood levels of interleukin-6 (IL-6), which is known to increase inflammation and the development of vascular disease and atherosclerosis. This study examined the hypothesis that ketosis increases the circulating levels of IL-6 in type 1 diabetic patients as well as the secretion of IL-6 in vitro in a cell culture model using U937 monocytes. RESEARCH DESIGN AND METHODS: Fasting blood was obtained from type 1 diabetic patients and healthy siblings. To examine the effect of ketosis, U937 monocytes were cultured with ketone bodies (acetoacetate [AA], beta-hydroxybutyrate [BHB]) in the presence or absence of high glucose levels in the medium at 37 degrees C for 24 h. IL-6 was determined by the sandwich enzyme-linked immunosorbent assay method, and intracellular reactive oxygen species (ROS) generation was detected using dihydroethidium dye. RESULTS: The blood level of IL-6 was higher in hyperketonemic (HK) diabetic patients than in normoketonemic (NK) diabetic patients (P < 0.05) and normal control subjects (P < 0.05). There was a significant correlation between ketosis and IL-6 levels (r = 0.36, P < 0.04, n = 34) in the blood of diabetic patients. Cell culture studies found that exogenous addition of the ketone body AA, but not BHB, increases IL-6 secretion and ROS generation in U937 cells. N-acetylcysteine (NAC) prevented the IL-6 secretion in acetoacetate-treated U937 monocytes. CONCLUSIONS: This study demonstrates that hyperketonemia increases IL-6 levels in the blood of type 1 diabetic patients and that NAC can inhibit IL-6 secretion by U937 monocytic cells cultured in a ketotic medium.
OBJECTIVE:Diabeticpatients have elevated blood levels of interleukin-6 (IL-6), which is known to increase inflammation and the development of vascular disease and atherosclerosis. This study examined the hypothesis that ketosis increases the circulating levels of IL-6 in type 1 diabeticpatients as well as the secretion of IL-6 in vitro in a cell culture model using U937 monocytes. RESEARCH DESIGN AND METHODS: Fasting blood was obtained from type 1 diabeticpatients and healthy siblings. To examine the effect of ketosis, U937 monocytes were cultured with ketone bodies (acetoacetate [AA], beta-hydroxybutyrate [BHB]) in the presence or absence of high glucose levels in the medium at 37 degrees C for 24 h. IL-6 was determined by the sandwich enzyme-linked immunosorbent assay method, and intracellular reactive oxygen species (ROS) generation was detected using dihydroethidium dye. RESULTS: The blood level of IL-6 was higher in hyperketonemic (HK) diabeticpatients than in normoketonemic (NK) diabeticpatients (P < 0.05) and normal control subjects (P < 0.05). There was a significant correlation between ketosis and IL-6 levels (r = 0.36, P < 0.04, n = 34) in the blood of diabeticpatients. Cell culture studies found that exogenous addition of the ketone body AA, but not BHB, increases IL-6 secretion and ROS generation in U937 cells. N-acetylcysteine (NAC) prevented the IL-6 secretion in acetoacetate-treated U937 monocytes. CONCLUSIONS: This study demonstrates that hyperketonemia increasesIL-6 levels in the blood of type 1 diabeticpatients and that NAC can inhibit IL-6 secretion by U937 monocytic cells cultured in a ketotic medium.
Authors: Douglas Ganini; Marcelo Christoff; Marilyn Ehrenshaft; Maria B Kadiiska; Ronald P Mason; Etelvino J H Bechara Journal: Free Radic Biol Med Date: 2011-05-08 Impact factor: 7.376
Authors: Marcin F Osuchowski; Florin L Craciun; Elizabeth Schuller; Corneliu Sima; Robert Gyurko; Daniel G Remick Journal: Shock Date: 2010-10 Impact factor: 3.454