Topical ocular levocabastine reduces ICAM-1 expression on epithelial cells both in vivo and in vitro.
Paraules clau
Resum
BACKGROUND
Levocabastine is a selective topical H1 antagonist, effective in the treatment of seasonal allergic rhinitis and conjunctivitis.
OBJECTIVE
We evaluated the possible effects of levocabastine eye drops on early (EPR) and late phase (LPR) inflammatory changes induced by allergen-specific conjunctival challenge (ASCC). We focused our attention on the possible effect of levocabastine on expression of the intracellular adhesion molecule-1 (ICAM-1) on epithelial cells. Such a phenomenon is likely to play an important role in allergic inflammation.
METHODS
The study was a double-blind, placebo-controlled, randomized trial, performed in cross-over, outside the pollen season. Ten out-patients suffering from allergic rhinoconjunctivitis due to parietaria judaica (wall parietary) were enrolled. Patients randomly received levocabastine 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 cytological 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 continuously cultured differentiated epithelial cell line (WK).
RESULTS
Levocabastine 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 inflammatory cell infiltration were only slightly modified by levocabastine 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 release by epithelium.
CONCLUSIONS
Levocabastine exerts anti-allergic activity, in that it reduces in vivo inflammatory cell infiltration due to ASCC, and also adhesion molecule expression on conjunctival epithelium. The latter phenomenon may be due, at least in part, to a direct effect of levocabastine on epithelial cells.
