No involvement of interleukin-5 or eosinophils in experimental allergic rhinitis in guinea pigs.
The aim of this study is to evaluate whether nasal airway eosinophilia is a true pathogenetic component of allergic rhinitis. We investigated the effects of TRFK5, an anti-interleukin-5 antibody, not only on leukocyte mobilization from the bone marrow, but also on the development of nasal symptoms and hyperresponsiveness in a guinea pig model of allergic rhinitis. Intranasally sensitized animals were repetitively challenged by exposure to Japanese cedar pollen as antigen. TRFK5 (100 microg/kg, i.p.) given 12 h before the final antigen challenge selectively prevented the antigen-induced eosinophilia in blood and the nasal airway, and suppressed the corresponding decrease in the number of cells in bone marrow; however, it failed to inhibit the immediate development of sneezing, early and late nasal blockage responses, goblet cell degranulation and nasal hyperresponsiveness to histamine. Furthermore, TRFK5 did not significantly affect the production of thromboxane A(2) and cysteinyl leukotrienes in the nasal airway during the late response. These results strongly suggest that while interleukin-5 is essential for eosinophil migration from the bone marrow to the nasal airway, neither interleukin-5 nor eosinophils are required for the development of the nasal symptoms and nasal hyperresponsiveness of allergic rhinitis.
Yamasaki
Masashi
M
Department of Pharmacology, Kyoto Pharmaceutical University, 5 Nakauchi, Misasagi, Yamashina, 607-8414, Kyoto, Japan. Yamasaki_Masashi@takeda.co.jp
Mizutani
Nobuaki
N
Sasaki
Kazutoyo
K
Nabe
Takeshi
T
Kohno
Shigekatsu
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D015550:Cell Degranulation; D003545:Cysteine / Q000032:analysis; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D020397:Goblet Cells / Q000276:immunology / Q000502:physiology; D006168:Guinea Pigs; D006632:Histamine / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D015289:Leukotrienes / Q000032:analysis; D008297:Male; D017817:Nasal Lavage Fluid / Q000737:chemistry / Q000166:cytology; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D015508:Nasal Obstruction / Q000276:immunology; D009299:Nasal Provocation Tests; D012220:Rhinitis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D012912:Sneezing / Q000276:immunology; D013929:Thromboxane B2 / Q000032:analysis
D000911:Antibodies, Monoclonal; D015848:Interleukin-5; D015289:Leukotrienes; C112381:cysteinyl-leukotriene; D013929:Thromboxane B2; D006632:Histamine; D003545:Cysteine