Human immunoglobulin preparations for intravenous use prevent endotoxin-induced uveitis in rats

We analyzed the preventive effect of immunoglobulins for intravenous use (IVIgs) in endotoxin-induced uveitis (EIU), a disease related to tumor necrosis factor alpha (TNF-alpha) production.

EIU was the experimental model in Lewis rats, injecting a systemic dose of 150 microg of lipopolysaccharide (LPS) into the rat's footpad. Half of them were treated with 5 serial intravenous doses of 100 mg of IVIg during the 5 days prior to LPS injection. Eyes were repeatedly examined with a slitlamp, rats were killed and their eyes enucleated for histopathologic study at the 2nd, 16th and 24th hours. TNF-alpha serum levels were measured in aqueous humor at several time intervals by a bioassay using L-929 mouse fibroblasts. Aqueous humor proteins were detected by the Bradford method.

IVIg treatment prevented EIU development, treated animals showing a lower grade of ocular inflammation beyond the 2nd hour (Fisher test, p > 0.05). Inflammatory cell infiltration was significantly reduced in the iris, ciliary body and anterior chamber at a 24-hour interval (Wilcoxon test, p < 0.05). This protection was associated with lower levels of TNF-alpha in serum at all time intervals and in aqueous humor at 16 h (Student's t test, p < 0.05), while differences were not significant between the samples of aqueous humor collected at 2 h. Protein exudate was not reduced in the treated group.

Repeated IVIg injections could be useful in the preventive treatment of EIU probably mediated by a decrease in TNF-alpha release.