Hyperglycemia and
inflammation are hallmarks of
burn injury. In this study, we used a rat model of
hyperglycemia and
burn injury to investigate the effects of
hyperglycemia on inflammatory responses in the liver.
Hyperglycemia was induced in male Sprague-Dawley rats with
streptozotocin (STZ) (35-40 mg/kg), followed by a 60% third-degree scald
burn injury.
Cytokine levels (by multiplex, in cytosolic
liver extracts),
hormones (by
enzyme-linked
immunosorbent assay [ELISA], in serum), nuclear factor (NF)-κB
protein deoxyribonucleic acid (
DNA) binding (by ELISA, in nuclear
liver extracts) and liver functional panel (using VetScan, in serum) were measured at different time points up to 7 d after
burn injury.
Blood glucose significantly increased after
burn injury in both groups with different temporal patterns. Hyperglycemic rats were capable of endogenous insulin secretion, which was enhanced significantly versus controls 12 h after
burn injury.
DNA binding data of liver nuclear extracts showed a robust and significant activation of the noncanonical NF-κB pathway in the hyperglycemic versus control
burn animals, including increased NF-κB-inducing
kinase expression (p < 0.05). Liver
acute-phase proteins and
cytokine expression were increased, whereas secretion of constitutive
proteins was decreased after
burn injury in hyperglycemic versus control animals (p < 0.05). These results indicate that
burn injury to the skin rapidly activated canonical and noncanonical NF-κB pathways in the liver. Robust activation of the NF-κB noncanonical pathway was associated with increased expression of inflammatory markers and
acute-phase proteins, and impaired
glucose metabolism.
Hyperglycemia is detrimental to
burn outcome by augmenting
inflammation mediated by hepatic noncanonical NF-κB pathway activation.