Modification of lipid A reduces endotoxin-induced eye effects

Intravenous endotoxin produces an acute toxic ocular reaction in rabbits. The core component of endotoxin, lipid A, can be modified by acid hydrolysis. This results in a detoxified ET that is relatively ineffective in inducing fever or lethal effects but which retains activity as a mitogen or as a cofactor in inducing tumor necrosis. We report that detoxified endotoxin was relatively ineffective in inducing iris hyperemia, increased ocular vascular permeability, a rise in aqueous humor prostaglandin E₂, or the generation of aqueous humor neutrophil chemotactic activity. Chemotactic activity was not increased in aqueous humor even though detoxified endotoxin effectively generated chemotactic activity from serum in vitro. These observations indicate the critical role of lipid A structure in producing ET-induced ocular effects and show that the ability of ET to act as a mitogen, induce tumor necrosis, or generate serum chemotactic activity can be dissociated from its ocular toxicity.