Metabolic response to endotoxin in vivo in the conscious mouse role of interleukin-6

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 mu g 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 +/- 07 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-alpha 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 (C) 2011 Elsevier Inc All rights reserved