ReviewPediatric research2015
Arginine depletion increases susceptibility to serious infections in preterm newborns.
Review in Pediatric research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 62 citations in OpenAlex.
- Enteral L-citrulline supplementation in preterm infants is safe and effective in increasing plasma arginine and citrulline levels-a pilot randomized trial.Journal of perinatology : official journal of the California Perinatal Association · 2024Trial
- T Cell- and Monocyte-Specific RNA-Sequencing Analysis in Septic and Nonseptic Critically Ill Patients and in Patients with Cancer.Journal of immunology (Baltimore, Md. : 1950) · 2019Trial
- Multi-omics insights into immunometabolic dysregulation in neonatal sepsis for precision medicine.Molecular biology reports · 2026Review
- Supplementary parenteral arginine corrects hypoargininaemia and rebalances plasma amino acid profiles in very preterm infants receiving parenteral nutrition: A prospective study.Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition · 2026Article
- Enteral and intravenous supplementation of arginine and citrulline fail to prevent necrotizing enterocolitis in preterm neonatal pigs.JPEN. Journal of parenteral and enteral nutrition · 2026Article
- Survival of the Littlest: Navigating Sepsis Diagnosis beyond Inflammation in Preterm Neonates.Journal of proteome research · 2025Article
- Pangolin scales as adaptations for innate immunity against pathogens.BMC biology · 2024Article
- Review
- Programmed and environmental determinants driving neonatal mucosal immune development.Immunity · 2023Review
- Immunonutrition: facilitating mucosal immune response in teleost intestine with amino acids through oxidant-antioxidant balance.Frontiers in immunology · 2023Review
- Perioperative arginine prevents metastases by accelerating natural killer cell recovery after surgery.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- The arginine deaminase system plays distinct roles in Borrelia burgdorferi and Borrelia hermsii.PLoS pathogens · 2022Article
- L-Arginine Depletion Improves Spinal Cord Injury via Immunomodulation and Nitric Oxide Reduction.Biomedicines · 2022Article
- Mining Anti-Inflammation Molecules FromFrontiers in cellular and infection microbiology · 2021Article
- Elimination of Hepatic RodentiScience · 2020Article
- IFN-γ Activates the TLR4-CCL5 Signaling Through Reducing Arginine Level, Leading to Enhanced Susceptibility of Bovine Mammary Epithelial Cells to Staphylococcus aureus.Inflammation · 2020Article
- L-Arginine Modulates Neonatal Leukocyte Recruitment in a Gestational Age-Dependent Manner.Journal of clinical medicine · 2020Article
- Erythroid Lineage Cells in the Liver: Novel Immune Regulators and Beyond.Journal of clinical and translational hepatology · 2020Review
- Severe Intestinal Dysbiosis in Rat Models of Short Bowel Syndrome with Ileocecal Resection.Digestive diseases and sciences · 2020Article
- Immunometabolic approaches to prevent, detect, and treat neonatal sepsis.Pediatric research · 2020Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.