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- Title
Elevated blood interleukin-6 levels in hyperketonemic type 1 diabetic patients and secretion by acetoacetate-treated cultured U937 monocytes.
- Authors
Jain, Sushil K.; Kannan, Krishnaswamy; Lim, Gideon; Matthews-Greer, Janice; McVie, Robert; Bocchini Jr., Joseph A.; Bocchini, Joseph A Jr
- Abstract
<bold>Objective: </bold>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.<bold>Research Design and Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
PEOPLE with diabetes; INFLAMMATION; VASCULAR diseases; ATHEROSCLEROSIS; ACETONEMIA
- Publication
Diabetes Care, 2003, Vol 26, Issue 7, p2139
- ISSN
0149-5992
- Publication type
journal article
- DOI
10.2337/diacare.26.7.2139