Arginine depletion increases susceptibility to serious infections in preterm newborns

Abstract

Preterm newborns are highly susceptible to bacterial infections. This susceptibility is regarded as being due to immaturity of multiple pathways of the immune system. However, it is unclear whether a mechanism that unifies these different, suppressed pathways exists. Here, we argue that the immune vulnerability of the preterm neonate is critically related to arginine depletion. Arginine, a “conditionally essential” amino acid, is depleted in acute catabolic states, including sepsis. Its metabolism is highly compartmentalized and regulated, including by arginase-mediated hydrolysis. Recent data suggest that arginase II-mediated arginine depletion is essential for the innate immune suppression that occurs in newborn models of bacterial challenge, impairing pathways critical for the immune response. Evidence that arginine depletion mediates protection from immune activation during first gut colonization suggests a regulatory role in controlling gut-derived pathogens. Clinical studies show that plasma arginine is depleted during sepsis. In keeping with animal studies, small clinical trials of L-arginine supplementation have shown benefit in reducing necrotizing enterocolitis in premature neonates. We propose a novel, broader hypothesis that arginine depletion during bacterial challenge is a key factor limiting the neonate's ability to mount an adequate immune response, contributing to the increased susceptibility to infections, particularly with respect to gut-derived sepsis.

Procalcitonin is a Better Biomarker than C-Reactive Protein in Newborns Undergoing Cardiac Surgery: The Prokineca Study

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“…This susceptibility is attributed to the immaturity of multiple immune pathways that are related to arginine depletion 18 . CD71+ erythroid cells suppress immune responses via arginase-2 activity 11 .…”

High Protein Intake Does Not Prevent Low Plasma Levels of Conditionally Essential Amino Acids in Very Preterm Infants Receiving Parenteral Nutrition

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