This study was conducted to investigate therapeutic value of a soluble
tumor necrosis factor-alpha (
TNF-alpha) receptor,
etanercept, in a rat model of
endotoxin-induced
uveitis (EIU). Forty-two inbred male Lewis rats were divided into seven equal groups. 200 microg of Escherichia coli 055:B55
lipopolysaccharide (LPS) was injected in one hind footpad of the Groups 2, 3, 4, 5, 6, and 7 rats. Group 5, 6, and 7 rats also received subcutaneous
etanercept 24 hr prior to LPS injection at a dose of 0.4 mg kg(-1). Group 1 rats were used as controls. Eight, 24, and 48 hr
after treatment clinical
uveitis scores (
miosis, iris
hyperemia, and hypopyon) were assessed by a masked observer and the rats were euthanized. Neutrophil leukocytes, CD8+, CD4+, and CD45RO+ cells in the anterior uveal tissue were counted either after
hematoxylin-
eosin or
monoclonal antibody staining.
TNF-alpha levels were also measured in the aqueous humor samples by an ELISA method.
Etanercept treatment significantly improved clinical
uveitis scores at all examination points compared to the LPS injected animals. The improvement was almost complete expect for the
miosis score, since no significant difference was detected between the controls and LPS +
Etanercept treated animals at all examination points. Cell counts were also at significantly lower levels in LPS +
Etanercept treated animals at all examination points, except for CD8+ and CD45RO+ cell counts at 24 hr examination point. There was no significant difference between the controls and LPS +
Etanercept treated animals at all examination points as with CD4+ and CD45RO+ cell counts at 48 hr. Our data showed that
etanercept had a definite effect on the treatment of EIU. Further studies should clarify its efficacy on clinical
uveitis conditions.