Dimethylthiourea inhibits the inflammatory response to intravitreally-injected endotoxin

Abstract

Dimethylthiourea, a potent scavenger of toxic oxygen metabolites such as the hydroxyl radical, hypochlorous acid, and hydrogen peroxide, was tested for its ability to inhibit an experimentally induced inflammatory response. Inflammation was induced in one eye of male New Zealand white rabbits by intravitreal injection of 10 ng Escherichia coli endotoxin; the contralateral eye received an equal volume of pyrogen-free saline vehicle. Dimethylthiourea was administered intraperitoneally to these animals at 0, 300, 450 and 600 mg kg-1. At 24 h post-endotoxin injection, all vehicle-injected eyes appeared normal with the exception of a small, but significant increase in aqueous humor protein concentration in the 600 mg kg-1 dimethylthiourea group. In endotoxin-injected eyes, treatment with dimethylthiourea, especially at the highest dose, significantly reduced iridal hyperemia, aqueous humor cell number and protein and prostaglandin-E concentrations, and the ex vivo release of prostaglandin-E from the lens. The ability of dimethylthiourea to significantly inhibit the inflammatory response to intravitreally-injected endotoxin suggests that toxic oxygen metabolites may play an important role in the initiation and/or propagation of this form of acute anterior uveitis. Furthermore, the data are consistent with an important interaction between toxic oxygen and arachidonic acid metabolites.