PURPOSE. To examine the potential therapeutic effect of a neutralizing anti
-IL-8 monoclonal antibody in endotoxin-induced uveitis (EIU) in the rabbit.
METHODS. An anti-IL-8 antibody (WS-4) was injected intra-vitreal 2 hours be
fore, simultaneously with, or 6 hours after endotoxin challenge in rabbits.
Eyes were examined for clinical signs of inflammation, and aqueous humor (
AH) was sampled to study cellular infiltration and protein content. Leukocy
te subset analysis was performed on Giemsa-stained AH cytospins. Histologic
grading of inflammation was performed on hematoxylin-eosin-stained sagitta
l sections of enucleated eyes. In separate experiments, animals received th
e anti-IL-8 antibody simultaneously with the endotoxin challenge, before re
peated anterior chamber paracentesis was performed (at 6, 12, 24, 48, and 7
2 hours after injection) to estimate the kinetics and durability of changes
in total cell count and protein concentration in AH.
RESULTS. Anti-IL-8 therapy caused a decrease in the clinical and histologic
grade of inflammation in EIU. The mean cell count in the AH at the peak of
-inflammation (34 hours) in eyes receiving endotoxin only was 6419 +/- 1165
/mu l (mean +/- SE) compared to 2546 +/- 573/mu l in rabbits treated simult
aneously with 250 mu g of anti-IL-8 antibody (P < 4.05). The protein concen
tration in the AH was not significantly altered by anti-IL-8 treatment. Kin
etic: analysis of the leukocyte count in the AH demonstrated persistent inh
ibition of leukocyte accumulation (range, 60%-91% compared to control eyes)
by the anti-IL-8 antibody administered simultaneously with endotoxin. This
inhibition was sustained for up to 72 hours after injection.
CONCLUSIONS. Anti-IL-8 antibody treatment partially blocks EIU in rabbits.
A consistent decrease in the recruitment of polymorphonuclear leukocytes in
to the anterior chamber was obtained when neutralizing antibody was injecte
d simultaneously with endotoxin. These findings suggest that IL-8 contribut
es to the chemotactic signal for the recruitment of leukocytes in EIU.