A lipid A analog ONO-4007 induces tolerance to plasma leakage in mice.
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.
Ishida
H
H
Department of Anesthesiology, Nippon Medical School, Tokyo, Japan.
Irie
K
K
Suganuma
T
T
Fujii
E
E
Yoshioka
T
T
Muraki
T
T
Ogawa
R
R
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
D008050:Lipid A; D008070:Lipopolysaccharides; C086889:ONO 4007; D003345:Corticosterone; D008797:Metyrapone