title: A lipid A analog ONO-4007 induces tolerance to plasma leakage in mice.
abstract: OBJECTIVE
  The effects of pretreatment with ONO-4007, a lipid A analog, on cutaneous plasma leakage induced by ONO-4007, lipopolysaccharide (LPS) and inflammatory mediators were investigated.
  
  
  METHODS
  Male ddY strain mice.
  
  
  METHODS
  Mice were pretreated with ONO-4007 (up to 6 mg/kg i.p.), 0-24 h prior to plasma leakage study.
  
  
  METHODS
  Plasma extravasation was determined by dye leakage.
  
  
  RESULTS
  Systemic ONO-4007 (6 mg/kg i. p.) pretreatment for 2 to 12 h inhibited plasma extravasation in the mouse skin elicited by ONO-4007 and LPS. The inhibition was dose-dependent. Plasma leakage induced by platelet-activating factor (PAF), histamine and 5-hydroxytryptamine (5-HT) was also inhibited by ONO-4007 pretreatment. Plasma corticosterone levels increased 2 and 4 h after systemic ONO-4007 (6 mg/kg) administration and returned to the control level 24 h later. Adrenalectomy and metyrapone but not propranolol reversed the inhibition by ONO-4007 pretreatment of LPS-induced plasma leakage.
  
  
  CONCLUSIONS
  A single injection of ONO-4007 in mice induced transient tolerance to plasma leakage elicited by LPS, ONO-4007 and inflammatory mediators. Endogenous corticosterone, at least in part, plays a role in the development of tolerance.
authors.affiliation: Department of Anesthesiology, Nippon Medical School, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ishida
authors.forename: K
authors.initials: K
authors.lastname: Irie
authors.forename: T
authors.initials: T
authors.lastname: Suganuma
authors.forename: E
authors.initials: E
authors.lastname: Fujii
authors.forename: T
authors.initials: T
authors.lastname: Yoshioka
authors.forename: T
authors.initials: T
authors.lastname: Muraki
authors.forename: R
authors.initials: R
authors.lastname: Ogawa
mesh_terms: D000311:Adrenal Glands / Q000502:physiology; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D003345:Corticosterone / Q000502:physiology; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D051379:Mice
chemical_list: D008050:Lipid A; D008070:Lipopolysaccharides; C086889:ONO 4007; D003345:Corticosterone; D008797:Metyrapone