IL-6 antagonizes TGF-beta and abolishes immune privilege in eyes with endotoxin-induced uveitis

Invest Ophthalmol Vis Sci. 2000 Aug;41(9):2591-9.


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)-beta, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and interferon (IFN)-gamma 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-beta 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-beta. 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-beta. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anterior Chamber / drug effects
  • Anterior Chamber / immunology
  • Aqueous Humor / drug effects*
  • Aqueous Humor / immunology
  • Blood-Aqueous Barrier / immunology
  • Cytokines / immunology
  • Female
  • Hypersensitivity, Delayed / immunology
  • Hypersensitivity, Delayed / prevention & control
  • Interleukin-6 / immunology
  • Interleukin-6 / pharmacology*
  • Lipopolysaccharides
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Salmonella typhimurium
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Transforming Growth Factor beta / antagonists & inhibitors*
  • Transforming Growth Factor beta / metabolism
  • Uveitis, Anterior / chemically induced
  • Uveitis, Anterior / immunology
  • Uveitis, Anterior / prevention & control*


  • Cytokines
  • Interleukin-6
  • Lipopolysaccharides
  • Transforming Growth Factor beta