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Title page for ETD etd-07282005-151919


Type of Document Master's Thesis
Author Tweedell, Andrea Donielle
Author's Email Address andrea.cedras@vanderbilt.edu
URN etd-07282005-151919
Title The impact of interleukin-6 on the metabolic response to endotoxin in vivo
Degree Master of Science
Department Molecular Physiology and Biophysics
Advisory Committee
Advisor Name Title
David Wasserman Committee Chair
Mary Courtney Moore Committee Member
Masakazu Shiota Committee Member
Owen McGuinness Committee Member
Keywords
  • Metabolism
  • Immunology
  • Sepsis
Date of Defense 2005-07-05
Availability unrestricted
Abstract
Inflammation and insulin resistance are characteristics of endotoxemia. While the role of interleukin-6 (IL-6) in insulin resistant states has been characterized, little is known of its role in the metabolic response to inflammation. To study the role of IL-6, conscious chronically catheterized mice were used. Five days prior to being studied, catheters were implanted in the carotid artery and jugular vein. After a 5 h fast, E.coli (250 microgram/mouse) LPS was injected in IL6-/- (KO; n=13), IL6+/- (HET; n=9), and IL-6+/+ (WT; n=10) littermates. The IL-6 response to LPS was simulated in an additional group of KO mice (KO+IL6; n=10). Glucose turnover (Ra) was assessed using 3-[3H]-D-glucose. IL-6 increased similarly in WT and HET (15±0.7 and 14±0.5 ng/ml) 4h after LPS and was undetectable in KO. IL-6 replacement in KO restored circulating IL-6 to levels observed in the WT group (14±0.3 ng/ml). WT was the only group to experience an early rise in tumor necrosis factor-alpha (TNF-alpha). Interleukin-1beta (IL-1beta) was similar in all groups. KO exhibited a more profound hyperglycemia 30 min after LPS injection and no apparent hypoglycemia at 4h (95±5 mg/dl). Glucose levels in KO+IL6, while decreased (93±4 mg/dl) at 4h, remained higher than WT. Ra was not altered. In summary, the absence of IL-6 protected against LPS induced hypoglycemia. Acute restoration of the IL-6 response to LPS did not potentiate hypoglycemia. Thus, while IL-6 promotes glucose intolerance in insulin resistant states, IL-6 promotes hypoglycemia during inflammation.
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