The effect of hyperglycemia on neonatal immune responses in-vitro

Abstract

Introduction. Acute hyperglycemia is considered as a pro-inflammatory state and is related to an adverse outcome in critically ill adults. Neonates are susceptible to infections and systemic inflammatory response syndrome induced by pro-inflammatory cytokines. This study focuses on the interaction between neonatal glucose homeostasis and the pro-inflammatory cytokine production in term and preterm infants in-vitro.

Methods. We analyzed the pro-inflammatory cytokine production in whole cord blood of term infants (n = 10), preterm infants > 32 weeks (n=16) and preterm infants ≤32 weeks of gestational age (n = 13) and in adult controls (n=14) using an in-vitro sepsis-model. Whole blood was pre-incubated with different concentrations of glucose (0–1000 mg/dl) and insulin (0–62.5 IE/l) and stimulated with lipopolysaccharide. The intracytoplasmatic TNF-α, IL-6, and IL-8 response was measured by flow cytometry.

Results. In-vitro hyperglycemia induced a dose-dependent increase of IL-8 in all age groups while TNF-α was demonstrated to be stimulated by glucose in cord blood samples of preterm infants ≤32 weeks of gestational age and term infants. In contrast, insulin showed no significant effects on pro-inflammatory cytokine production in-vitro.

Conclusion. Acute hyperglycemia may induce pro-inflammatory cytokine responses in neonatal whole blood in-vitro. These data provide a basis for further in-vitro signal transduction studies and in-vivo investigations about the significance of neonatal glucose homeostasis and its impact on long-term outcome of this susceptible patient cohort.

Keywords::

• Neonatal
• cytokines
• flow cytometry
• endocrine immunology

Acknowledgment

This work was supported by “Lübeck Hilfe für krebskranke Kinder, e.V.”, Lübeck und Possehl Stiftung, Lübeck.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.