title: Role of acute-phase proteins in interleukin-1-induced nonspecific resistance to bacterial infections in mice.
abstract: Treatment with a single low dose (80 to 800 ng) of interleukin-1 (IL-1) 24 h before a lethal bacterial challenge of granulocytopenic and normal mice enhances nonspecific resistance. Since IL-1 induces secretion of acute-phase proteins, liver proteins which possess several detoxifying effects, we investigated the role of these proteins in the IL-1-induced protection. Inhibition of liver protein synthesis with D-galactosamine (GALN) completely inhibited the IL-1-induced synthesis of acute-phase proteins. GALN pretreatment abolished the protective effect of IL-1 on survival completely (neutropenic mice infected with Pseudomonas aeruginosa) or partially (nonneutropenic mice infected with Klebsiella pneumoniae). Pretreatment with IL-6, a cytokine induced by IL-1, did not reproduce the protection offered after IL-1 pretreatment, nor did it enhance or deteriorate the IL-1-enhanced resistance to infection. A protective effect of IL-1 via effects on glucose homeostasis during the acute-phase response was investigated by comparing plasma glucose levels in IL-1-treated mice and control mice before and during infection. Although glucose levels in IL-1-pretreated mice were somewhat higher in the later stages of infection, no significant differences from levels in control mice were present, and the glucose levels in control-treated animals never fell to hypoglycemic values. We conclude that the IL-1-induced nonspecific resistance is mediated neither by the induction of IL-6 nor by the effects of IL-1 on glucose homeostasis. Acute-phase proteins generated after IL-1 pretreatment, however, seem to play a critical role in the IL-1-induced protection to infection.
authors.affiliation: Department of Medicine, University Hospital, Nijmegen, The Netherlands.
authors.forename: M T
authors.initials: MT
authors.lastname: Vogels
authors.forename: L
authors.initials: L
authors.lastname: Cantoni
authors.forename: M
authors.initials: M
authors.lastname: Carelli
authors.forename: M
authors.initials: M
authors.lastname: Sironi
authors.forename: P
authors.initials: P
authors.lastname: Ghezzi
authors.forename: J W
authors.initials: JW
authors.lastname: van der Meer
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000276:immunology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury; D004305:Dose-Response Relationship, Drug; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005688:Galactosamine / Q000494:pharmacology / Q000633:toxicity; D006706:Homeostasis / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015850:Interleukin-6 / Q000502:physiology; D007710:Klebsiella Infections / Q000097:blood / Q000276:immunology*; D007711:Klebsiella pneumoniae; D008107:Liver Diseases / Q000201:enzymology; D051379:Mice; D011552:Pseudomonas Infections / Q000097:blood / Q000276:immunology*
chemical_list: D000209:Acute-Phase Proteins; D001786:Blood Glucose; D007375:Interleukin-1; D015850:Interleukin-6; D005688:Galactosamine; D005340:Fibrinogen