The effects of fexofenadine on eosinophilia and systemic anaphylaxis in mice infected with Trichinella spiralis.
BACKGROUND
The effects of the non-impairing, H(1)-receptor antagonist fexofenadine were investigated in in vivo mouse models of eosinophilia and systemic anaphylaxis.


METHODS
Eosinophilia was investigated in C57BL/6 mice (n=5 per group) infected with Trichinella spiralis, with and without administration of fexofenadine HCl (5, 10 and 20 mg/kg/day). Eosinophilia was also studied, with and without fexofenadine administration, in mice with a congenital mast-cell deficiency (W/W(v)) and controls (+/+). The effect of fexofenadine HCl (20 mg/kg/day) on IL-5 and eotaxin blood levels was also investigated in C57BL/6 mice. In a separate model, systemic anaphylaxis was induced in C57BL/6 mice using T. spiralis antigen. Fexofenadine HCl (5, 10 and 20 mg/kg) or vehicle was administered 20 min before antigen challenge (n=5 per group). The effect of fexofenadine on systemic anaphylaxis caused by IgE and anti-IgE was also examined in CBF1 mice injected with serum from NC/Nga mice with high IgE levels. Rectal temperature was measured as an indicator of anaphylaxis.


RESULTS
In C57BL/6 mice, repetitive oral administration of fexofenadine HCl (5, 10 and 20 mg/kg/day) resulted in dose-dependent suppression of eosinophilia (p<0.05-0.0001). No suppression was observed in mast-cell deficient W/W(v) mice. In addition, single oral administration of fexofenadine HCl (10 and 20 mg/kg) significantly suppressed the decrease in rectal temperature (p<0.01), a marker for systemic anaphylaxis, in C57BL/6 mice. In CBF1 mice injected with serum from NC/Nga mice with high IgE levels, the decrease in rectal temperature was suppressed by single administration of fexofenadine HCl (10 and 20 mg/kg; p<0.01 and p<0.001, respectively). Fexofenadine had no effect on peripheral IL-5 and eotaxin levels.


CONCLUSIONS
These results indicate that fexofenadine suppresses both eosinophilia and systemic anaphylaxis, both of which are fundamental reactions in allergic diseases.
Watanabe
Naohiro
N
Department of Tropical Medicine, Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato, Tokyo 105-8461, Japan. naohiro@jikei.ac.jp
Matsuda
Emiko
E
Masuda
Akiko
A
Nariai
Koichi
K
Shibasaki
Toshiaki
T
D000707:Anaphylaxis / Q000188:drug therapy* / Q000209:etiology; D000818:Animals; D000947:Antigens, Helminth / Q000737:chemistry; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000032:analysis; D004802:Eosinophilia / Q000188:drug therapy* / Q000209:etiology; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015848:Interleukin-5 / Q000097:blood; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology; D051379:Mice; D013045:Species Specificity; D016593:Terfenadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D017160:Trichinella spiralis; D014235:Trichinellosis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology
D000947:Antigens, Helminth; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D004731:Endotoxins; D006634:Histamine H1 Antagonists; D015848:Interleukin-5; D016593:Terfenadine; C093230:fexofenadine