Effect of FK506 eye drops on late and delayed-type responses in ocular allergy models.
BACKGROUND
It is well-known that FK506 strongly inhibits cytokine production by T cells in vitro. However, less evidence is available from in vivo studies of ocular allergy.


OBJECTIVE
To study the anti-inflammatory effect of FK506 eye drops on late and delayed-type responses in several animal models of ocular allergy.


METHODS
Rats and guinea-pigs were sensitized with egg albumin (EA) in adjuvant and later challenged by topical EA application to their eyes to examine the late response. Biopsy specimens of conjunctiva were stained with haematoxylin-eosin or stained for T cells and eosinophils. In addition, rats, rabbits and guinea-pigs were sensitized with complete Freund's adjuvant and later challenged by injecting purified protein derivatives for the delayed-type response. Bulbar conjunctival oedema and hyperaemia were graded by score in rabbits, and Evans blue (EB) extravasation was measured in rats and guinea-pigs. FK506 (0.01-1%) and steroid (0.1%) eye drops were instilled in the eyes of animals several times, before and after challenge.


RESULTS
FK506 eye drops inhibited T cell and eosinophil infiltration in the late response and EB extravasation in the delayed-type response in rats. Also, they inhibited conjunctival oedema, hyperaemia and ocular mucus in the delayed-type response in rabbits. These effects were similar to those of steroid eye drops (betamethasone sodium phosphate, fluorometholone). FK506 eye drops also inhibited inflammatory cell infiltration, the loss of conjunctival epithelium and decrease of goblet cells in the late response as well as EB extravasation in the delayed-type response in guineapigs, a steroid-resistant species.


CONCLUSIONS
FK506 eye drops inhibit late and delayed-type responses in animal models of ocular allergy.
Sengoku
T
T
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Kashima, Yodogawa-ku, Osaka, Japan. takanori_sengoku@po.fujisawa.co.jp
Sakuma
S
S
Satoh
S
S
Kishi
S
S
Ogawa
T
T
Ohkubo
Y
Y
Mutoh
S
S
D000818:Animals; D003233:Conjunctivitis, Allergic / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004804:Eosinophils / Q000276:immunology; D005938:Glucocorticoids / Q000627:therapeutic use; D006168:Guinea Pigs; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D009883:Ophthalmic Solutions; D011817:Rabbits; D051381:Rats; D011914:Rats, Inbred BN; D013601:T-Lymphocytes / Q000276:immunology; D016559:Tacrolimus / Q000627:therapeutic use*
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D009883:Ophthalmic Solutions; D016559:Tacrolimus