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

Abstract: Topical application of plasmid DNA en-coding 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) re-actions 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 applica-tion 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- in-duction for antiangiogenesis. In contrast, exposure of GKO mice to IP-10 DNA did suppress the se-verity of HSK. Furthermore, treatment with spe-cific antisera to IP-10 and MIG in HSV-infected mice abrogated the IL-12-induced inhibitory effect on lesion severity. Taken together, our data indi-cate that the HSV-induced ocular immunoinflam-matory 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 agains