Evaluation of nasal barrier dysfunction at acute- and late-phase reactions in a guinea pig model of allergic rhinitis.
Allergic rhinitis is a common disease characterized by the symptoms of pruritus, sneezing, hypersecretion and nasal blockage. Increased mucosal barrier permeability has been suggested to be an indicator for the severity of allergic rhinitis. This study investigates the passage of radiolabelled albumin from the nasal mucosal circulation into the lumen in guinea pigs intraperitoneally sensitized and intranasally challenged with antigen. In order to characterize the allergic rhinitis model, we evaluated a number of potential influencing factors in nasal plasma exudation, including antigen doses, volumes of antigen solution used, and animal position during the nasal lavage, and the conditions of nasal lavage. The number of eosinophils and levels of histamine and leukotriene B4 in the nasal lavage and eosinophils in the nasal mucosa were determined at the early and late phases after antigen challenge. We also compared the effects of topical nasal treatments for allergic rhinitis on nasal inflammatory responses. Our results demonstrate that, in the guinea pig nasal mucosa, topical challenge with antigens induces plasma exudation and histamine release at the acute-phase reaction, and plasma exudation and eosinophil infiltration at the late-phase reaction. These changes are similar to those reported in human allergic rhinitis. Alterations of nasal plasma exudation, histamine release and eosinophil influx were dependent upon the concentrations and volumes of antigens. An antihistamine inhibited the acute-phase reaction partially, whereas budesonide inhibited effects at the late-phase reaction. We suggest that this model of guinea pig allergic rhinitis with the early and late responses may be useful for high-throughout screening of new drugs.
Elovsson
Sofia
S
Department of Clinical Study Management, AstraZeneca R&D Lund, Sweden.
Smailagic
Amir
A
Erjefalt
Ingrid
I
Zackrisson
Catharina
C
Eriksson
Christina
C
Wang
Xiangdong
X
D000287:Administration, Topical; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004804:Eosinophils / Q000648:ultrastructure; D005122:Exudates and Transudates / Q000187:drug effects; D006168:Guinea Pigs; D006632:Histamine / Q000097:blood; D007975:Leukotriene B4 / Q000097:blood; D008407:Mast Cells / Q000648:ultrastructure; D008854:Microscopy, Electron; D017817:Nasal Lavage Fluid / Q000166:cytology; D009297:Nasal Mucosa / Q000503:physiopathology*; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy / Q000503:physiopathology*
D018926:Anti-Allergic Agents; D007975:Leukotriene B4; D006632:Histamine