IL-12 suppresses the expression of ocular immunoinflammatory lesions by effects on angiogenesis.
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-gamma 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-gamma 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.
Lee
Sujin
S
Department of Microbiology, Walters Life Sciences Building, University of Tennessee, Knoxville, TN 37996-0845, USA.
Zheng
Mei
M
Deshpande
Shilpa
S
Eo
Seong Kug
SK
Hamilton
Thomas A
TA
Rouse
Barry T
BT
D000818:Animals; D003315:Cornea / Q000098:blood supply*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D018259:Herpesvirus 1, Human; D018664:Interleukin-12 / Q000235:genetics / Q000627:therapeutic use*; D016849:Keratitis, Herpetic / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000628:therapy*; D010957:Plasmids / Q000627:therapeutic use
D016207:Cytokines; D018664:Interleukin-12