title: Impaired energy metabolism during neonatal sepsis: the effects of glutamine.
abstract: Neonatal sepsis is an important cause of morbidity and mortality as a result of multiple organ system failure, particularly in neonates requiring total parenteral nutrition. Suitable therapies and support are needed both to prevent sepsis and to prevent multiple organ failure. After bacterial infection, pro-inflammatory cytokines trigger the antimicrobial activity of macrophages and neutrophils, resulting in production of reactive species such as H2O2, NO, superoxide and peroxynitrite. However, excess production can lead to host tissue damage. Incubation of either hepatocytes or heart mitochondria from neonatal rats with these reactive species, or with cytokines, leads to impairment of mitochondrial oxidative function, and in an animal model of neonatal sepsis similar results to the in vitro findings have been demonstrated. Recent in vivo studies, using indirect calorimetry of suckling rat pups, show that during endotoxaemia there is a profound hypometabolism, associated with hypothermia. Having determined that cellular oxidative function may be impaired during sepsis, it is of great importance to try to identify therapeutic measures. Much interest has been shown in glutamine, which may become essential during sepsis. It has been shown that hepatic glutamine is rapidly depleted during endotoxaemia. When hepatocytes from endotoxaemic rats were incubated with glutamine, there was a restoration of mitochondrial structure and metabolism. In vivo, intraperitoneal injection of glutamine into endotoxic suckling rats partially reversed hypometabolism, markedly reduced the incidence of hypothermia and improved clinical status. These results suggest that glutamine has a beneficial effect during sepsis in neonates.
authors.affiliation: Surgery Unit and Biochemistry, Endocrinology and Metabolism Unit, Institute of Child Health (University College London), 30 Guilford Street, London WC1N 1EH, UK. s.eaton@ich.ucl.ac.uk
authors.forename: Simon
authors.initials: S
authors.lastname: Eaton
mesh_terms: D000818:Animals; D000833:Animals, Suckling; D001481:Basal Metabolism / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000188:drug therapy* / Q000378:metabolism; D004734:Energy Metabolism; D005973:Glutamine / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D051381:Rats; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism; D022722:Thermogenesis / Q000187:drug effects / Q000502:physiology
chemical_list: D005973:Glutamine