Effects of cyclosporin A and glucocorticosteroids on antigen-induced hypersensitivity to histamine in a guinea pig model of allergic rhinitis.
OBJECTIVE
In an attempt to study the pathogenesis of mucosal hypersensitivity in allergic rhinitis, we investigated the suppressive effects of cyclosporin A (CyA) and glucocorticosteroids on ovalbumin (OA)-induced hypersensitivity to topical histamine challenge.


METHODS
Actively sensitized Dunkin-Hartley guinea pigs.


METHODS
OA and alum were applied to guinea pigs intraperitoneally 3 times at two-week intervals. After general sensitization, OA inhalation was performed every day for 6 days as topical sensitization. Before inhalation, treatment with CyA (50 mg/kg, p.o.), glucocorticosteroids (beclomethasone propionate (1.0 mg/kg, i.p.), fluticasone propionate (FP, 0.5 mg/kg, i.p.)) or vehicle were performed, and the sensitivity to histamine was measured before and after the inhalation. Moreover, in actively (general and topical) sensitized guinea pigs, FP (0.5 mg/kg, i.p.) was applied every day for 5 days and histamine sensitivity was evaluated before and after the application.


RESULTS
We found that histamine sensitivity was significantly increased by nasal antigen challenge in this guinea pig model, and that the occurrence of histamine hypersensitivity was inhibited by the pretreatment with CyA and glucocorticosteroids. Although multiple administration of FP gradually reduced the histamine hypersensitivity according to the period of administration, it did not significantly alter the histamine hypersensitivity after the occurrence of hypersensitivity.


CONCLUSIONS
It is concluded that CyA and glucocorticosteroids suppress antigen-induced histamine hypersensitivity in a guinea pig model of allergic rhinitis.
Narita
S I
SI
Department of Medicine, McMaster University, Hamilton, Ont., Canada. naritas@fhs.McMaster.ca
Asakura
K
K
Shiraski
H
H
Isobe
M
M
Ogasawara
H
H
Saito
H
H
Kataura
A
A
D000280:Administration, Inhalation; D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001507:Beclomethasone / Q000008:administration & dosage / Q000627:therapeutic use; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004342:Drug Hypersensitivity / Q000188:drug therapy* / Q000209:etiology; D000068298:Fluticasone; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006168:Guinea Pigs; D006632:Histamine; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D008297:Male; D010047:Ovalbumin; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy* / Q000209:etiology
D000730:Androstadienes; D018926:Anti-Allergic Agents; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D006632:Histamine; D016572:Cyclosporine; D010047:Ovalbumin; D000068298:Fluticasone; D001507:Beclomethasone