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IL‐12 suppresses the expression of ocular immunoinflammatory lesions by effects on angiogenesis
Author(s) -
Lee Sujin,
Zheng Mei,
Deshpande Shilpa,
Eo Seong Kug,
Hamilton Thomas A.,
Rouse Barry T.
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.71.3.469
Subject(s) - angiogenesis , biology , herpes simplex virus , corneal neovascularization , chemokine , immunology , neovascularization , keratitis , lesion , cornea , cytokine , immunosuppression , cancer research , inflammation , virus , pathology , medicine , genetics , neuroscience
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‐γ 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‐γ 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.