Cytokine expression in vivo during murine herpetic stromal keratitis. Effect of protective antibody therapy.
HSV-1 topical infection on the murine cornea can induce herpetic stromal keratitis (HSK), a T cell-mediated inflammatory response that results in blindness. To begin to decipher the molecular interactions involved in this infection, extracts of infected corneas were assayed for the presence of seven different cytokines by ELISA. The most prominent cytokines detected were IL-1 alpha and IL-6. Both were elevated by day 2 after infection, reached peak levels of 82 and 538 pg/cornea, respectively, at day 10, and then diminished over the next 10 days. In contrast, TNF-alpha concentrations were not elevated over that seen in uninfected corneas at any time during the 20-day observation period. IFN-gamma and granulocyte-macrophage CSF corneal concentrations were below the sensitivity of the assay. We investigated whether passive transfer of antibody to viral glycoprotein D, which prevents HSK, influenced the production of IL-1 alpha and IL-6. It was found that corneal concentrations of IL-1 alpha were reduced threefold and IL-6 was undetectable at day 10 in the antibody-treated hosts. The levels of IL-10 and IL-4 in uninfected control and antibody-treated hosts were also monitored. Neither of these two regulatory cytokines was associated with HSK development or effective antibody therapy. Naive corneas cultured in vitro spontaneously produced IL-1 and IL-6, indicating that cells resident in the cornea had the ability to synthesize these proinflammatory cytokines. Collectively, our results imply that IL-1 alpha and IL-6 may be important contributors to the development of HSK pathogenesis.
Department of Microbiology and Immunology, University of South Alabama College of Medicine, Mobile 36688.
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Staats
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Lausch
D000818:Animals; D000914:Antibodies, Viral / Q000008:administration & dosage*; D003315:Cornea / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D007167:Immunotherapy; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016849:Keratitis, Herpetic / Q000503:physiopathology* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D018139:Simplexvirus / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000914:Antibodies, Viral; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4