TOPICAL OCULAR LEVOCABASTINE REDUCES ICAM-1 EXPRESSION ON EPITHELIAL-CELLS BOTH IN-VIVO AND IN-VITRO

Background Levocabastine is a selective topical H-1 antagonist, effect ive in the treatment of seasonal allergic rhinitis and conjunctivitis. Objective We evaluated the possible effects of levocabastine eye drop s on early (EPR) and late phase (LPR) inflammatory changes induced by allergen-specific conjunctival challenge (ASCC). We focused our attent ion on the possible effect of levocabastine on expression of the intra cellular adhesion molecule-1 (ICAM-1) on epithelial cells. Such a phen omenon is likely to play an important role in allergic inflammation. M ethods The study was a double-blind, placebo-controlled, randomized tr ial, performed in cross-over, outside the pollen season. Ten out-patie nts suffering from allergic rhinoconjunctivitis due to Parietaria juda ica (wall parietary) were enrolled. Patients randomly received levocab astine eye drops (0.5 mg/mL) or placebo eyedrops, one drop in the left eye (right eye as control), 30 min before ASCC. Clinical evaluation ( hyperaemia, burning-itching, lacrimation and eyelid swelling) and cyto logical assessment (number of neutrophils, eosinophils and lymphocytes , and ICAM-1 expression on conjunctival epithelium) were evaluated at baseline, 30 min and 6 h after ASCC. In parallel, we evaluated the in vitro effect of levocabastine at concentrations ranging from 2 x 10(-9 ) M to 2 x 10(-5) M on ICAM-1 expression and shedding by a continuousl y cultured differentiated epithelial cell line (WK). Results Levocabas tine reduced symptom scores during EPR (15 min and 30 min, P < 0.002), inflammatory cell infiltration during EPR (P < 0.002 for neutrophils, eosinophils and lymphocytes) and ICAM-1 expression on epithelium both during EPR (P < 0.002) and LPR (P < 0.02). LPR symptom scores and inf lammatory cell infiltration were only slightly modified by levocabasti ne treatment. In vitro levocabastine at 2 x 10(-5) M concentration was able to down-regulate basal ICAM-1 expression, although it exerted no effect on ICAM-1 expression by interferon-gamma (IFN gamma)-stimulate d WK cells and on soluble ICAM-1 release by epithelium. Conclusion Lev ocabastine exerts anti-allergic activity, in that it reduces in vivo i nflammatory cell infiltration due to ASCC, and also adhesion molecule expression on conjunctival epithelium. The latter phenomenon may be du e, at least in part, to a direct effect of levocabastine on epithelial cells.