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


METHODS
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.


RESULTS
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.


CONCLUSIONS
Repeated IVIg injections could be useful in the preventive treatment of EIU probably mediated by a decrease in TNF-alpha release.
Obrador
E
E
División de Oftalmología, Facultad de Medicina, Universidad Miguel Hernandez, Alicante, España.
Peinado
E
E
de Kozak
Y
Y
Ruiz-Moreno
J M
JM
Alio
J L
JL
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D002829:Choroid / Q000473:pathology; D002924:Ciliary Body / Q000473:pathology; D005136:Eye Proteins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007498:Iris / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D051381:Rats; D011917:Rats, Inbred Lew; D012160:Retina / Q000473:pathology; D012486:Salmonella typhimurium; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014605:Uveitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
D005136:Eye Proteins; D016756:Immunoglobulins, Intravenous; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha