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Robin R. Fenton, Sara Molesworth-Kenyon, John E. Oakes, Robert N. Lausch; Linkage of IL-6 with Neutrophil Chemoattractant Expression in Virus-Induced Ocular Inflammation. Invest. Ophthalmol. Vis. Sci. 2002;43(3):737-743.
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purpose. Herpes simplex virus (HSV)-1 infection of the murine cornea is known to
stimulate a vigorous interleukin (IL)-6 response, but whether this
pleiotropic cytokine is an essential participant in corneal
inflammation is unclear. This study was designed to compare the early
inflammatory response in IL-6 gene-deficient mice to that in wild-type
methods. Gene knockout and wild-type mice (C57BL/6 background) were infected
intracorneally with HSV-1 (strain RE) and observed through clinical
examination and immunohistochemistry for the development of corneal
opacity. Virus corneal titers were determined by standard plaque assay
on Vero cells. Cytokine and chemokine levels in corneal lysates were
measured with commercial ELISA kits.
results. Corneal opacity in IL-6−/− mice was substantially
diminished in comparison with IL-6+/+ hosts 24 to 48 hours
after intracorneal viral infection, and corneal levels of (MIP)-2 and
MIP-1α were significantly reduced. Local administration of IL-6 at
the time of infection restored corneal opacity and chemokine levels to
that of wild-type hosts. Antibody neutralization of endogenous IL-6 in
IL-6+/+ animals reduced corneal opacity scores and MIP-2
levels to that of IL-6−/− mice. Ex vivo studies with
excised corneal buttons revealed that uninfected IL-6−/− corneas injected with IL-6 produced MIP-2 and MIP-1α at levels
comparable to that seen in IL-6+/+ hosts.
conclusions. Collectively, these results suggest that IL-6 promotes corneal
inflammation by acting in an autocrine–paracrine fashion to induce
resident corneal cells to make MIP-2 and MIP-1α, which in turn
recruit neutrophils to the virus infection site.
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