Mechanisms for Glucocorticoid Inhibition of Immediate Hypersensitivity Reactions in Rats.
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概要
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The inhibitory mechanisms of immediate hypersensitivity reactions by glucocorticoid (GC) were studied in rats. Homologous passive cutaneous anaphylaxis (PCA) mediated by IgE anti-bodies and cutaneous reactions caused by histamine, serotonin and leukotriene C<SUB>4</SUB> were elicited at the same time in the same rats. Three kinds of GC, hydrocortisone, prednisolone and dexamethasone, inhibited all these reactions significantly. Although mediator-induced cutaneous reactions were inhibited transiently around 2 hours after GC administration, inhibition of PCA was more potent and lasted longer. A time lag seemed to be essential for both inhibitions. IgE antibody-mediated histamine release in vivo in the rat peritoneal cavity was also inhibited by GC administration significantly, and the inhibition was long lasting when compared to those of the mediator-induced cutaneous reactions. Tyrosine amino-transferase (TAT) activity in the rat liver increased significantly by GC administration, and the in creased TAT activity was completely abrogated by simultaneous administration of 5 mg/kg of cyclohex imide (CH). In the same experimental condition, although inhibition of histamine-induced cutaneous reaction by GC was completely abrogated, the inhibition of PCA elicited at the same time in the same rats was only partially attenuated. Furthermore, the same dose of CH little affected the dexamethasone inhibition of histamine release in the rat peritoneal cavity, although the increase of TAT activity in the liver of the same rats was completely abrogated. These results demonstrate that PCA is inhibited by GC through at least 2 mechanisms, inhibition of mediator release from mast cells and non-specific inhibition of vascular permeability increase caused by released mediators. Although the latter action of GC is dependent upon protein synthesis, the former seems to be mediated by a unique mechanism independent of protein synthesis.
- 公益社団法人 日本薬理学会の論文
著者
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Koda Akihide
Department Of Pharmacology Gifu College Of Pharmacy
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Miura Toru
Department Of Biology Graduate School Of Arts And Sciences University Of Tokyo
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Nakajima Takashi
Department Network And Computer Engineering School Of Information And Design Engineering Tokai Unive
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Inagaki Naoki
Departmen T Of Pharmacology Gifu Pharmaceutical University
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Nagai Hiroichi
Department Of Applied Pharmacology Graduate School Of Medicine And Pharmaceutical Sciences University Of Toyama
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Yoshida Kenji
Department of Biochemistry, Kinki University School of Medicine
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Nakajima Takashi
Department of Pharmacology, Gifu Pharmaceutical University
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