Establishment of T-helper type 2 clone-induced eosinophilia in mouse conjunctiva.
Eosinophil infiltration is one of the aspects of the inflammatory response to an allergen. The aim of this study was to establish T-helper type-2 (Th2)-induced conjunctival eosinophilia in mice to evaluate the effect of anti-allergic drugs. Th2 clone, D10.G4.1. (D10) with its specific antigen, conalbumin was co-injected into conjunctival tissue in mice. At 3-6 hr after D10 injection, eosinophil and neutrophil recruitment into conjunctival tissue was observed. Cellular infiltration into conjunctival tissue reached a maximum level between 24-48 hr after D10 injection. The number of eosinophils which infiltrated after 24 hr was dose dependent on T cell injection titer from 1x10(4), 1x10(5)to 1x10(6)cells site-1. The ratio of eosinophils to neutrophils at 24 hr after D10 cell (1x10(5)cells site-1) injection was about 9 to 1. The eosinophil infiltration into conjunctival tissue was significantly reduced by the intraperitoneal administration of anti-IL-5 monoclonal antibody (100 micrograms animal-1). Anti-IL-4 monoclonal antibody (500 micrograms animal-1) partially inhibited eosinophilia. The combined inhibitory effect of anti-IL-4 and anti-IL-5 monoclonal antibodies was larger than the inhibitory effect of anti-IL-5 monoclonal antibody alone. In conclusion, a Th2-induced mouse conjunctival eosinophilia model was established in which D10 activation results in IL-4 and IL-5 release. These cytokines elicit eosiniophil infiltration. This response shows that the model will be effective for screening candidates of anti-allergic drugs.
Hamada
M
M
Ophthalmic Research Division, Santen Pharmaceutical Co., Ltd., 8916-16 Takayama-cho, Ikoma-shi, 630-0101, Japan.
Sawa
K
K
Nakata
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D003233:Conjunctivitis, Allergic / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology* / Q000473:pathology; D005260:Female; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D051379:Mice; D008806:Mice, Inbred AKR; D018418:Th2 Cells / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015848:Interleukin-5; D015847:Interleukin-4