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(Journal of Leukocyte Biology. 2002;71:469-476.)
© 2002 by Society for Leukocyte Biology

IL-12 suppresses the expression of ocular immunoinflammatory lesions by effects on angiogenesis

Sujin Lee^*, Mei Zheng^*, Shilpa Deshpande^*, Seong Kug Eo^*, Thomas A. Hamilton and Barry T. Rouse^*

^* Department of Microbiology, University of Tennessee, Knoxville; and
Department of Immunology, Cleveland Clinic Foundation, Ohio

Correspondence: Dr. Barry T. Rouse, Department of Microbiology, M409 Walters Life Sciences Building, University of Tennessee, Knoxville, TN 37996-0845. E-mail: btr{at}utk.edu

Topical application of plasmid DNA encoding IL-12 to the cornea of mice prior to ocular infection with Herpes simplex virus type 1 (HSV) results in diminished corneal immunoinflammatory lesions. Such herpetic stromal keratitis (HSK) reactions in humans represent an important cause of blindness. The effect of IL-12 pretreatment acted via inhibitory effects on corneal neovascularization rather than by inhibiting viral replication or the function of CD4⁺ T cells that mediate HSK. The antiangiogenesis induced by IL-12 DNA application was mediated indirectly via the cytokine IFN- and one or both of two chemokine molecules, IP-10 and MIG. Thus IL-12 DNA administration lacked modulatory effects on HSK in GKO mice, indicating the necessary involvement of IFN- induction for antiangiogenesis. In contrast, exposure of GKO mice to IP-10 DNA did suppress the severity of HSK. Furthermore, treatment with specific antisera to IP-10 and MIG in HSV-infected mice abrogated the IL-12-induced inhibitory effect on lesion severity. Taken together, our data indicate that the HSV-induced ocular immunoinflammatory lesions can be modulated by IL-12 and that this effect results from chemokine inhibition of angiogenesis. The use of antiangiogenesis therapy might represent a useful control measure against HSK.

Key Words: herpetic stromal keratitis • chemokine • cytokine • immunopathology

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