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Manju J. Verma, Naofumi Mukaida, Ute Vollmer–Conna, Kouji Matsushima, Andrew Lloyd, Denis Wakefield; Endotoxin-Induced Uveitis is Partially Inhibited by Anti–IL-8 Antibody Treatment. Invest. Ophthalmol. Vis. Sci. 1999;40(11):2465-2470.
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purpose. To examine the potential therapeutic effect of a neutralizing
anti–IL-8 monoclonal antibody in endotoxin-induced uveitis (EIU) in
methods. An anti–IL-8 antibody (WS-4) was injected intravitreal 2 hours before,
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. Leukocyte subset analysis was performed on Giemsa-stained AH
cytospins. Histologic grading of inflammation was performed on
hematoxylin-eosin–stained sagittal sections of enucleated eyes. In
separate experiments, animals received the anti–IL-8 antibody
simultaneously with the endotoxin challenge, before repeated anterior
chamber paracentesis was performed (at 6, 12, 24, 48, and 72 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 (24 hours) in eyes receiving endotoxin only was
6419 ± 1165/μl (mean ± SE) compared to 2546 ±
573/μl in rabbits treated simultaneously with 250 μg of anti–IL-8
antibody (P < 0.05). The protein concentration in the AH was
not significantly altered by anti–IL-8 treatment. Kinetic analysis of
the leukocyte count in the AH demonstrated persistent inhibition 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
into the anterior chamber was obtained when neutralizing antibody was
injected simultaneously with endotoxin. These findings suggest that
IL-8 contributes to the chemotactic signal for the recruitment of
leukocytes in EIU.
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