Anti-allergic action of glucocorticoids in rats.

Japanese Journal of Pharmacology

Yoshida

et al. 1992

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ABSTRACT-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 C4 were elicited at the same time in the same rats. Three kinds of GC, hydrocortisone, prednisolone and dexamethasone, in hibited 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 long er. 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 in hibition 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 in dependent of protein synthesis.

Section: Discussionsupporting

confidence: 85%

mentioning

confidence: 99%

Mechanisms for Glucocorticoid Inhibition of Immediate Hypersensitivity Reactions in Rats

Miura

Japanese Journal of Pharmacology

Yoshida

et al. 1992

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“…All these results suggest that mouse ear PCA might be a useful method for evaluating antianaphylactic agents like rat homologous PCA in the back skin [1][2][3].…”

mentioning

confidence: 87%

“…In the ear, PCA reaction was more sensitive and reproducible than that in the dorsal skin. The reaction was significantly suppressed by ketotifen, one of antianaphylactic agents.Passive cutaneous anaphylaxis (PCA) reaction [9] is one of the most useful methods for evaluating anti anaphylactic agents [1][2][3]. In mice, PCA reaction was usually elicited in dorsal skin and the activity of antianaphylactic agents was evaluated by means of reduced dimension or diameter of PCA site [4], In our preliminary experiment, however, the PCA reaction in dorsal skin of mice was little reproducible.…”

mentioning

confidence: 99%

Mouse Ear PCA as a Model for Evaluating Antianaphylactic Agents

Int Arch Allergy Immunol

Goto

Nagai

et al. 1984

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“…These results suggest a possibility that the vascular permeability inhibitory protein plays an important role in the inhibition of the PCA and the skin reactions observed in the pres ent study. However, Nagai et al [ 10] indicated that the IgE antibody-mediated rat homologous PCA is inhi bited by glucocorticoids with a latent period of about 1 h but that antiglucocorticoids [24, 30] do not influ ence the inhibition. Furthermore, a protein synthesis inhibitor, actinomycin D, also failed to recover the in hibition of the rat homologous PCA [unpubl.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Vascular Permeability Increase in Mice

Int Arch Allergy Immunol

Miura²,

Nagai³

et al. 1988

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Effects of glucocorticoids on IgE antibody-mediated 48-hour homologous passive cutaneous anaphylaxis (PCA) and skin reactions caused by mediator releasers and vascular permeability increasing factors were investigated comparatively. Both PCA and skin reactions were evoked in the mouse ear and these reactions were quantitatively evaluated by measuring the amount of dye extravasated into the ear. The glucocorticoids hydrocortisone, prednisolone and dexamethasone inhibited the PCA significantly. The maximum inhibitory effects of these glucocorticoids were obtained when administered 8 h prior to the antigenic challenge. Dexamethasone significantly inhibited the skin reactions caused by compound 48/80, Ca ionophore A 23187 and hypotonic salt solution. Dexamethasone also significantly inhibited the skin reactions caused by histamine, serotonin, platelet-activating factor, leukotriens C₄ and D₄, and bradykinin. The maximum inhibitory effects of dexamethasone on these skin reactions were observed when administered 12–6 h before. These results support the previous observations that glucocorticoids inhibit the increase of vascular permeability caused by various stimuli, and indicate that the inhibition of vascular permeability increase contributes at least in part to the inhibitory effects on the PCA and the mediator releaser-induced skin reactions. Furthermore, the inhibition of vascular permeability increase by glucocorticoids might play an important role in their anti-allergic actions.