Endotoxin-induced uveitis in the rat. A study of the role of inflammation mediators.

Intraocular inflammation was induced in the rat by footpad injection of salmonella endotoxin in order to study the influence of chemical inflammation mediators in this uveitis model. Ocular inflammation was assessed 1, 6, 18, 24 and 72 h after endotoxin administration as well as in control rats, by measuring aqueous protein concentration, aqueous inflammatory cell content, and pupillary diameter. Thromboxane B2 (TXB2), prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2-alpha), leukotriene B4 (LTB4), and substance P were simultaneously measured in the aqueous humor by radioimmunoassay. Inflammation parameters peaked at 18 h. TXB2 was already significantly elevated at 1 h. PGE2 peak values of 2.7 ng/ml were reached at 18 h. PGF2-alpha was never significantly raised over control values. LTB4 peaked at 18 h, together with a polymorphonuclear peak. Substance P was significantly elevated after 6 h. It is concluded that maximal uveitis in this model occurs at 18 h. TXB2 is an early mediator, and PGE2 is probably implicated in blood-ocular barrier disruption for which levels as high as 2.7 ng/ml in aqueous seem necessary. PGF2-alpha does not play a major role in this model, while LTB4 seems to be the main chemotactic factor for polymorphonuclears (PMNs) in the anterior chamber and substance P is clearly related to pupil miosis.