Prednisolone inhibits an IgE-mediated late-phase allergic cutaneous reactionby interfering with the activation of mast cells in mice.
Epicutaneous antigen challenge in passively sensitized mice with IgE produces a biphasic cutaneous response which peaks 1 h (immediate-phase reaction) and 24 h (late-phase reaction; LPR) after the antigen challenge. In this model, anaphylactic degranulation and interleukin 6 (IL-6) expression between 4 and 8 h are observed in resident mast cells as the preceding stage of LPR. Prednisolone at a dose of 3 mg kg(-1) clearly inhibited the LPR when administered 2 h before and 4 h after antigen challenge. Slight or no inhibition of LPR was observed by prednisolone administered 6-12 h after challenge. Histologically, prednisolone treatment 2 h before antigen challenge completely inhibited edema and inflammatory cell infiltration, while treatment at 6 h did not at all. In order to investigate the relationship between inhibition of LPR by prednisolone and mast cell activation, the effects of prednisolone on degranulation of mast cells and IL-6 expression in mast cells were investigated. 8 h after antigen challenge, prednisolone clearly inhibited the increase in the number of anaphylactic degranulated and IL-6-positive mast cells by administration 2 h before challenge, but did not affect it by administration 6 h after challenge. These data indicate that the inhibitory mechanism of prednisolone on LPR, at least, involves the inhibition of mast cell activation before LPR.
Kimata
M
M
Department of Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
Abe
T
T
Yamaguchi
I
I
Mito
K
K
Tsunematsu
M
M
Inagaki
N
N
Nagai
H
H
D000818:Animals; D015550:Cell Degranulation; D004139:Dinitrofluorobenzene / Q000276:immunology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000276:immunology; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000096:biosynthesis; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D011239:Prednisolone / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors
D005938:Glucocorticoids; D015850:Interleukin-6; D007073:Immunoglobulin E; D011239:Prednisolone; D004139:Dinitrofluorobenzene