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Beatriz E. Brito, Leslie M. O’Rourke, Yuzhen Pan, Joy Anglin, Stephen R. Planck, James T. Rosenbaum; IL-1 and TNF Receptor–Deficient Mice Show Decreased Inflammation in an Immune Complex Model of Uveitis. Invest. Ophthalmol. Vis. Sci. 1999;40(11):2583-2589.
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purpose. To determine the role of interleukin-1 (IL-1) and tumor necrosis
factor-α (TNF-α) in the induction of uveitis by a reverse passive
Arthus reaction (RPAR).
methods. Human serum albumin (HSA) antiserum was injected into the vitreous of“
knockout” or “double knockout” mice genetically deficient in
IL-1 receptor type I (IL-1RI-/-), TNF receptors p55 and p75
(TNFR p55-/-/p75-/-), IL-1RI and TNFR p55
(IL-1RI-/-/TNFR p55-/-), and controls.
Twenty-four hours later, animals were challenged with intravenous HSA.
Eyes were enucleated 4 hours after antigen challenge, and inflammation
was quantitated by counting cells on histologic sections. Interleukin-6
in aqueous humor was measured with a B9 cell bioassay. The distribution
of immune complexes in eyes was observed by immunohistochemical
staining for IgG and complement component C3.
results. Four hours after antigen challenge, immune complexes were localized at
the ciliary body and iris of receptor-deficient mice. A transient
uveitis was most severe at this time. A significant reduction in the
median number of infiltrating cells was found in TNFR
p55-/-/p75-/- mice (4.8, n = 15), compared with controls (14.2, n = 20, P < 0.05). The median number of infiltrating cells
was significantly reduced in IL-1RI-/- mice (knockout 2.6, n = 11; controls 7.4, n = 8, P < 0.005). Interleukin-1RI-/-/TNFR
p55-/- mice had a strong reduction in infiltrating cells
(knockout 1.6, n = 11; controls 27.3, n = 12, P = 0.002).
Interleukin-6 activity in aqueous humor was reduced in
IL-1RI-/-/TNFR p55-/- mice
(P = 0.03) but not in TNFR
p55-/-/p75-/- (P = 0.40)
mice. Most IL-1RI-/- mice had no detectable aqueous humor
IL-6, but this group was not statistically different from controls.
conclusions. In contrast to endotoxin-induced uveitis, both IL-1 and TNF appear to
have critical roles in RPAR uveitis. When receptors for these cytokines
were deleted, the severity of immune complex–induced uveitis was
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