Bench-to-bedside review: Neonatal sepsis - redox processes in pathogenesis

Ivan Spasojević,Budimir Obradović,Snežana Spasić

doi:10.1186/cc11183

Abstract

The present review is aimed at elucidating the neonatal 'sepsis redox cycle' - the cascade of inflammatory and redox events involved in the pathogenesis of sepsis in neonates. While adult and neonatal sepses share some common features, there are some substantial differences: higher mortality rates occur in adult sepsis and worse long-term effects are evident in neonatal sepsis survivors. Such epidemiological data may be explained by the lower ability of IL6 and IL8 to activate NF-κB-regulated transcription in neonatal sepsis in comparison to TNF-α, which is involved in the mechanisms of adult sepsis. The activation of NF-κB in neonatal sepsis is further promoted by hydrogen peroxide and results in mitochondrial dysfunction and energy failure as septic neonates experience decreased O2 consumption as well as lower heat production and body temperature in comparison to healthy peers. In neonates, specific organs that are still under development are vulnerable to sepsis-provoked stress, which may lead to brain, lung, and heart injury, as well as vision and hearing impairments. In the light of the processes integrated here, it is clear that therapeutic approaches should also target specific steps in the neonatal 'sepsis redox cycle' in addition to the current therapeutic approach that is mainly focused on pathogen eradication.

Highlights

Sepsis is a devastating health problem taking millions of lives every year in neonatal ICUs (NICUs) all around the world [1,2]
AWe extracted and pooled the results provided in the manuscript and performed statistical analysis using Statistica 6.0 (StatSoft, Inc., Tulsa, OK, USA); statistical significance was determined by the means of non-parametric two-tailed Mann-Whitney test. fMPL, N-formyl-methionyl-leucyl-phenylalanin; IFN, interferon; O, superoxide; PMA, phorbol 12-myristate 13-acetate; ROS, reactive oxygen species
While the neonatal ‘sepsis redox cycle’ in most cells types may lead to reversible dysfunction, in others that are proliferating and sensitive to oxidative stress, it may initiate apoptosis, which seems to account for most morbidities found following a neonatal sepsis episode

Summary

Introduction

Sepsis is a devastating health problem taking millions of lives every year in neonatal ICUs (NICUs) all around the world [1,2]. Two studies have been performed on hepatocytes obtained from rat neonates very early in sepsis (2 hours after LPS injection), showing that there is no significant decrease in ATP levels [67,69] This may be due to the ability of neonatal cells to compensate for mitochondrial dysfunction by extra-mitochondrial ATP production [67]. While the neonatal ‘sepsis redox cycle’ in most cells types may lead to reversible dysfunction, in others that are proliferating and sensitive to oxidative stress, it may initiate apoptosis, which seems to account for most morbidities found following a neonatal sepsis episode

Conclusion

Baltimore RS

80. Crouser ED

Findings

86. Volpe JJ