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Updated: Jul 28, 2026
Intralymphatic Immunotherapy and Vaccination in Mice
Published on: February 2, 2014
A lipid A analog ONO-4007 induces tolerance to plasma leakage in mice
1Department of Anesthesiology, Nippon Medical School, Tokyo, Japan.
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.
Material:
Male ddY strain mice.
Treatment:
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.
