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Kouichi Ohta, Satoru Yamagami, Andrew W. Taylor, J. Wayne Streilein; IL-6 Antagonizes TGF-β and Abolishes Immune Privilege in Eyes with Endotoxin-Induced Uveitis. Invest. Ophthalmol. Vis. Sci. 2000;41(9):2591-2599.
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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)-β, tumor
necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and interferon
(IFN)-γ 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-β 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-β.
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-β. 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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