Reduced parenteral glucose supply during neonatal infection attenuates neurological and renal pathology associated with modulation of innate and Th1 immunity

Abstract

Background

Premature infants are highly susceptible to infections that can lead to sepsis with life-threatening organ dysfunctions. The clinical practice of high parenteral glucose supply in preterm infants can exacerbate infection outcomes through excessive glycolysis-induced inflammatory response. This in turn can affect the health of vital preterm organs, including the brain and kidneys. We hypothesized that reduced parenteral glucose supply to infected preterm newborns may help protect against pathology in these two key organs.

Methods

Cesarean-delivered preterm pigs were nourished with high or low parenteral glucose levels (21 % vs. 5 %), infused with Staphylococcus epidermidis or saline, and monitored in heated, oxygenated incubators until 22 h. Blood, brain, and kidney samples were collected for histological, immunohistological, q-PCR, ELISA, and biochemical analyses.

Results

Infection led to multiple pathological changes (e.g. edema), increased inflammation and tissue injury (indicated by gene expression data) in both brain and kidneys of preterm piglets. Reduced glucose supply in infected animals alleviated histopathological manifestations in the brain, and reduced neuroinflammation with enhanced M2 microglial phenotype. Reduced glucose supply also decreased plasma creatinine, and the severity of renal edema, tubular vacuolization and dilatation. Multiple genes related to innate and Th1 immunity in both organs were dampened by reduced glucose supply. Correlation analysis showed that renal inflammation was more closely connected to systemic inflammation compared to neuroinflammation.

Conclusion

Reduced glucose supply can reduce renal and neuro-inflammation during neonatal infection, thereby protecting brain and kidney health in infected preterm neonates.