Elevated levels of prostaglandin E(2) in the tears of patients with severe allergic conjunctivitis and primary cultured conjunctival cells are suppressed by ketotifen and dexamethasone

OBJECTIVE: We examined the production of prostaglandin E(2) (PGE(2)), which is the key prostaglandin involved in inflammatory disorders of the ocular surface. Tears and conjunctival fibroblasts were evaluated in order to assess allergic inflammation and the effect of specific drugs. METHODS AND ANALYSIS: PGE(2) was measured in tears from both patients and normal volunteers. Primary cultures of human conjunctival fibroblasts were incubated with interleukin (IL)-4 and tumour necrosis factor (TNF)-α with or without ketotifen fumarate or dexamethasone. The culture supernatants were removed 24 hours after exposure and the concentrations of PGE(2) were quantified by ELISA. RESULTS: Significantly higher levels of PGE(2) were observed in the tears of patients with severe allergic conjunctivitis than in those with post-surgical inflammation (p=0.02), and this production was reduced by eye drops. Stimulation with IL-4 and TNF-α induced the generation of PGE(2) in supernatants of conjunctival fibroblasts, and this production was significantly downregulated by ketotifen fumarate or steroids. CONCLUSION: PGE(2) may participate in the pathogenesis of severe ocular allergic disease, and both ketotifen fumarate and steroid reduce the production of PGE(2).