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1 From the Institut National de la Santé et de la Recherche Médicale, Unite 450, Development, Aging and Pathology of the Retina; and the 2 Department of Ophthalmology, Hôpital Pitié-Salpêtrière, Paris, France.
PURPOSE. Interleukin (IL)-13 is a strong immunomodulatory cytokine that inhibits macrophages from secreting proinflammatory mediators. This study was conducted to investigate the effect of intraocular injection of IL-13 on the development of endotoxin-induced uveitis (EIU) in the Lewis rat.
METHODS. One injection into the anterior chamber of recombinant human IL-13 (6 ng in 10 µl saline) was performed either simultaneously with a single injection of lipopolysaccharide (LPS) from Salmonella typhimurium into the footpad or 6 hours before the IL-13 injection. EIU was evaluated by slit lamp examination at 6, 16, and 24 hours after LPS injection. Counts of inflammatory cells were performed on cryostat sections after specific immunostaining. Anterior chamber paracentesis was performed, and kinetic analysis of the IL-13 injected in the anterior chamber was performed by ELISA. Cytokine and chemokine gene expression in the iris-ciliary body and the retina was evaluated by reverse transcription–polymerase chain reaction.
RESULTS. A significant inhibition of ocular inflammation was observed in
IL-13–treated rats at 16 and 24 hours after LPS injection. Unilateral
injection of IL-13 inhibited EIU only in the injected eye. High levels
of IL-13 were detected in the aqueous humor at 2 hours after local
IL-13 injection to remain high up to 18 hours. In contrast, IL-13 was
not detected in the corresponding sera. Quantitative analysis of
inflammatory cells in ocular tissues showed a significant decrease in
OX-42+ cells (microglia, activated macrophages, dendritic
cells, and polymorphonuclear leukocytes) and ED1+ cells
(monocytes-macrophages and dendritic cells) in treated rats. A
decreased expression of TNF-
, IL-1ß, IL-6, monocyte
chemoattractant protein (MCP)-1, and macrophage inflammatory protein
(MIP)-2 mRNAs was observed in the iris-ciliary body and the retina from
IL-13–treated rats, whereas IFN-
was upregulated in the
iris-ciliary body.
CONCLUSIONS. Injection of IL-13 into the anterior chamber may inhibit the ocular inflammation induced by LPS injection by reducing intraocular cytokine and chemokine mRNA expression in ocular tissues.
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