title: Metabolic response to endotoxin in vivo in the conscious mouse: role of interleukin-6.
abstract: Inflammation and insulin resistance are characteristics of endotoxemia. Although the role of interleukin (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 before being studied, catheters were implanted in the carotid artery and jugular vein. After a 5-hour fast, Escherichia coli (250 μg per mouse) lipopolysaccharide (LPS) was injected in IL-6⁻/⁻ (KO, n = 13) and IL-6+/+ (WT, n = 10) littermates. The IL-6 response to LPS was simulated in an additional group of KO mice (KO + IL-6, n = 10). Interleukin-6 increased in WT (15 ± 0.7 ng/mL) 4 hours after LPS and was undetectable in KO. Interleukin-6 replacement in the KO restored circulating IL-6 to levels observed in the WT group (14 ± 0.3 ng/mL). Tumor necrosis factor-α increased more rapidly in WT than in both KO and KO + IL-6 mice. The KO mice exhibited a more profound glucose excursion 30 minutes after LPS injection and no apparent hypoglycemia at 4 hours (95 ± 5 vs 70 ± 8 mg/dL, KO vs WT), despite having a blunted glucagon and epinephrine response. Glucose levels in KO + IL-6 mice, while decreased (93 ± 4 mg/dL) at 4 hours, remained higher than those in WT mice. 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 but partially restored the glucagon response. Thus, although IL-6 promotes glucose intolerance in insulin-resistant states, IL-6 promotes hypoglycemia during acute inflammation.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt Univ. School of Medicine, Nashville, TN 37232-0615, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tweedell
authors.forename: Kimberly X
authors.initials: KX
authors.lastname: Mulligan
authors.forename: Josie E
authors.initials: JE
authors.lastname: Martel
authors.forename: Fu-Yu
authors.initials: FY
authors.lastname: Chueh
authors.forename: Tammy
authors.initials: T
authors.lastname: Santomango
authors.forename: Owen P
authors.initials: OP
authors.lastname: McGuinness
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000097:blood; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D002395:Catecholamines; D007328:Insulin; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D005934:Glucagon; D005947:Glucose