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From the Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
PURPOSE. To determine the immunosuppressive status of aqueous humor (AqH) from mouse eyes afflicted with endotoxin-induced uveitis (EIU) and to identify the relevant cytokines responsible for immunomodulatory activity within EIU AqH.
METHODS. Bacterial lipopolysaccharide (LPS) was injected into hind footpads of
C3H/HeN mice; and AqH, collected at 6, 12, 24, and 48 hours, was
evaluated for content of transforming growth factor (TGF)-ß, tumor
necrosis factor (TNF)-
, interleukin (IL)-1ß, IL-6, and interferon
(IFN)-
and capacity to suppress anti-CD3–driven T-cell
proliferation. Cytokine mRNA expression in iris–ciliary body (I/CB)
was analyzed by RNase protection assays.
RESULTS. During 6 to 24 hours after LPS injection, total TGF-ß levels in AqH increased even though the fluid lost its capacity to suppress T-cell activation. At this time, AqH contained high levels of IL-6, and I/CB contained high levels of IL-6 mRNA. When IL-6 was neutralized with specific antibodies, inflamed AqH reacquired its capacity to suppress T-cell activation, which correlated with high levels of TGF-ß. Coinjection of IL-6 plus antigen into the anterior chamber of the eye of normal mice prevented antigen-specific anterior chamber–associated immune deviation (ACAID).
CONCLUSIONS. LPS-induced intraocular inflammation is associated with local production of IL-6, which robs AqH of its immunosuppressive activity, perhaps by antagonizing TGF-ß. The fact that IL-6 antagonized ACAID induction in normal eyes suggests that strategies to suppress the intraocular synthesis of IL-6 may reduce inflammation and restore ocular immune privilege.
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