Elevated levels of prostaglandin E₂in the tears of patients with severe allergic conjunctivitis and primary cultured conjunctival cells are suppressed by ketotifen and dexamethasone

Abstract

ObjectiveWe examined the production of prostaglandin E2 (PGE2), 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 analysisPGE2 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 PGE2 were quantified by ELISA.ResultsSignificantly higher levels of PGE2 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 PGE2 in supernatants of conjunctival fibroblasts, and this production was significantly downregulated by ketotifen fumarate or steroids.ConclusionPGE2 may participate in the pathogenesis of severe ocular allergic disease, and both ketotifen fumarate and steroid reduce the production of PGE2.

Ocular surface itch and pain: key differences and similarities between the two sensations

“…Results showed a statistically significant elevation ( P < 0.04) in the average tear PGE2 level in VKC patients (190 pg/ml) compared to control subjects (6.0 pg/ml). After a 4-week treatment of ketotifen fumarate and dexamethasone, the PGE2 levels were reduced in the VKC patients to a mean of 62.6 pg/ml ( P < 0.04), along with a decrease in symptoms [15]. These findings suggest that molecules involved in allergic processes contribute to ocular itch in individuals with allergic ocular surface disease.…”

Concentrations of PGE2 and TXB2 in the Eyes of Mice with Disseminated Acanthamoebiasis

“…Yamanishi et al [24] found decreased production of PGE 2 in the tears of patients with severe conjunctivitis after dexamethasone administration. Fuller et al [40] reported that dexamethasone inhibits the production of thromboxane B 2 .…”

“…infection are associated with an ongoing inflammatory process. The proteins involved in this process are PGs, products of the reaction carried out by cyclooxygenases [23,24]. Under normal physiological conditions, PGs have crucial homeostatic functions, including maintaining IOP.…”

Therapeutic Targets in Allergic Conjunctivitis

“…Leukotriene is a lipid mediator that causes vasodilation and increased permeability of conjunctival blood vessels [ 61 , 62 , 63 ]. Prostaglandin has been shown to intensify the ocular itch and cause dilation of conjunctival blood vessels [ 64 , 65 ]. Cytokines are small, secreted cell-signaling proteins that are released by both immune and non-immune cells.…”