Suppression of experimental immune-mediated blepharoconjunctivitis in Brown Norway rats by topical application of FK506.
BACKGROUND
Experimental immune-mediated blepharoconjunctivitis (EC) in Brown Norway (BN) rats, which is inducible by transfer of antigen-specific T cells, is a model for human allergic conjunctivitis. We investigated the possible inhibition of EC in BN rats by topical application of FK506, which is an immunosuppressive agent that mainly targets T cells.


METHODS
To induce EC by active immunization, ovalbumin (OVA) adsorbed to alum was injected into the hind footpads of BN rats. Three weeks after the initial immunization, rats were challenged with OVA by eye drops. Twenty-four hours later, lids including conjunctivas, lymph nodes (LNs), and sera were harvested for histology or reverse transcriptase PCR, proliferation assays, and measurement of IgE titer, respectively. For passive immunization, rats were intravenously injected with 10 million of in vitro-stimulated OVA-primed LN cells. Four days after the transfer, rats were challenged with OVA and evaluated as above. The rats were divided into two groups. One group received topical FK506 treatment three times per day from 15 to 21 days after active immunization or from 1 to 4 days after transfer. The other group was treated with vehicle as above.


RESULTS
FK506 treatment suppressed infiltration of both lymphocytes and eosinophils in the conjunctiva either by active or passive immunization (P<0.002). No differences were noted in antigen-specific cellular and humoral immune responses. Concerning cytokine expression in the conjunctiva, a prominent difference was noted only with IL-4, which was more abundantly detected in the vehicle-treated group.


CONCLUSIONS
Topical FK506 treatment suppressed EC in BN rats, possibly by inhibition of IL-4 in the conjunctiva.
Nishino
Koji
K
Department of Ophthalmology, Kochi Medical School, Nankoku, Japan.
Fukushima
Atsuki
A
Okamoto
Shigeki
S
Ohashi
Yuichi
Y
Fukata
Kazuyo
K
Ozaki
Akemi
A
Ueno
Hiasyuki
H
D000287:Administration, Topical; D000818:Animals; D001762:Blepharitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003231:Conjunctivitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D007116:Immunization, Passive; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D009883:Ophthalmic Solutions; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D009883:Ophthalmic Solutions; D010047:Ovalbumin; D016559:Tacrolimus