The effect of corticosteroids or nitrogen mustard on aqueous humor chemotactic activity induced by intravitreal endotoxin.

In rabbits intravitreal injection of endotoxin induces potent chemotactic activity for monocytes in aqueous humor. We have assessed the effect of methylprednisolone (30 mg/kg intramuscularly) or nitrogen mustard (1.75 mg/kg intravenously) on the generation of this chemotactic activity. Histologic changes, anterior chamber protein extravasation, and aqueous humor cellular infiltration were reduced by corticosteroids to a variable degree. However, even in animals with a marked reduction in protein extravasation or histologic change, chemotactic activity was substantially preserved. Similarly, nitrogen mustard induced a leukopenia without affecting the ability of endotoxin to generate chemotactic activity in aqueous humor. In contrast, corticosteroids reduced both protein extravasation and the generation of chemotactic activity induced by intravenously injected endotoxin. The results suggest that the chemotactic activity induced in the eye by intravitreal endotoxin may be locally synthesized and may be present without a substantial leukocytic infiltrate.

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.