Effects of topical FK506 on experimental allergic conjunctivitis

Abstract

In vitro studies of FK506 demonstrated that the agent inhibited the T-cell receptormediated signal transduction that results in the transcription of interleukin 2. Recent in vitro studies have demonstrated an identical spectrum of activities of FK506 on IgE receptor-mediated signal transduction that results in exocytosis of secretory granules from basophils and mast cells. The effects of topical FK506 on allergic conjunctivitis were therefore studied in the rat. Passive anaphylaxis was induced in Wistar rats by injecting anti-ovalbumin IgE at the conjunctiva followed by intravenous injection of antigen (ovalbumin) and Evans blue. Topical FK506 (0.03-0.1%) significantly suppressed the passive anaphylaxis in the rat conjunctiva when given at 15 and five minutes, or six, four and two hours before the antigen challenge. The efficacy was more intense than that of 0.1% betamethasone or 2% disodium cromoglycate. These data thus suggest that topical FK506 might be beneficial for the therapy of severe allergic diseases in the eye.

Key Words:

• immunophilin ligands
• FK506
• mast cell
• experimental allergic conjunctivitis
• rat