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Background Azelastine is a selective Hi-receptor antagonist. which has previously been demonstrated to he effective in the treatment of allergic rhinitis. We have recently demonstrated that nasal azelastine inhibits the clinical anti inflammatory events following nasal allergen challenge. Particularly, we focused our attention on [CAM-I expression on epithelial cells, since it is the natural ligand of LEA-I. an adhesion molecule expressed by leucocytes, including eosinophils. Objective Since azelastine ocular drops are now available, the aim of the present study was the evaluation of the anti-allergic activity in the model of allergen specific conjunctival challenge (ASCC). Methods Twenty outpatients with allergic rhinoconjunctivitis due to Parietaria Judaica (Wall Parietary) were included outside the pollen season. The study was designed as randomized. placebo-controlled, double-blind and parallel group. developed in two parts. The former investigated the onset of effect of a single dose of azelastine eye drops administered 20 min after clinical response due to ASCC. The latter evaluated the clinical and inflammatory parameters following ASCC after 7-days treatment with azelastine. Clinical parameters (hyperaemia. itching. lacrimation and eyelid swelling) were evaluated at baseline. 5. 10, 20 and 30 min (i.e. early phase reaction-EPR) and 6 h (i.e. late phase reaction-LPR) after ASCC. Cytological assessment (number of neutrophils, cosinophils, monocytes and lymphocytes) and ICAM-1 expression on conjunctival epithelial cells were evaluated at baseline, 30 min (i.e. early phase reaction-EPR) and 6 h (i.e. late phase reaction-LPR after ASCC. Results When administered 30 min after ASCC, azelastine produced a clinical effect ranging between 10 and 20 min after eye drops administration (P <0.01). After 7 days of treatment, 30 min after ASCC, azelastinc induced a reduction of symptom scores during EPR and LPR (P <0.01), a reduction of inflammatory cell infiltration during both EPR (P < 0.01) and LPR (P < 0.01). and a reduction of ICAM-I expression during EPR and LPR (both P < 0.01), Placebo did not modify any of the studied parameters. Conclusion. Azelastine eye drops exert anti-allergic activity, inducing a rapid improvement of clinical events when administered after ASCC, and reducing both symptoms and cellular infiltration when administered before ASCC. Finally, azelastine down-regulates ICAM-I expression on epithelial conjunctival cells, confirming the results obtained at nasal level. [ABSTRACT FROM AUTHOR]

Background Ievocabastine is a selective topical H 1 antagonist, effec-tive 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 chal-lenge (ASC'C). 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 eye drop one drop in the left eye (right eye as control). 30 min before ASCC. Clinical evaluation (hyperaemia, burning-itching. lacrimation and eyelid swelling) and phytological assessment (number of neutrophils. eosinophils and lymphocytes. and ICAM- I 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 concen-trations ranging from 2 x 109 M to 2 x 105 M on ICAM-l expression and shedding by a continuously cultured differentiated epithelial cell line (WK). Results Levocabastine reduced symptom scores during EPR (1 5 min and 30 mm. P> 0.002). inflammatory cell infiltration during EPR (P> 0.002 for neutro-phils. eosinophils and lymphocytes) and ICAM- I 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 10-5M concentration was able to down regulate basal ICAM -1 expression. although it exerted no effect on ICAM-l expre-ssion by interferon γ(IFNγ)stimulated WK cells and on soluble ICAM- I release by epitheliurn. Conclusion: 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. [ABSTRACT FROM AUTHOR]