Interleukin-17 enhanced immunoinflammatory lesions in a mouse model of recurrent herpetic keratitis

Interleukin-17 (IL-17), mainly produced by activated (memory) T cells, has been found in the corneas from herpetic stromal keratitis (HSK) patients. To better understand the role of IL-17 and to optimize fidelity to human recurrent HSK, in this study, we utilized a mouse model of recurrent HSK, examined the expression of IL-17 and Th17 cells, and determine the alterability of virus-induced corneal inflammation after anti-IL-17 antibody treatment during murine recurrent HSK. We found that Th17 cells were obviously up-regulated in both cornea and DLNs of recurrent mice. Peak IL-17 protein present in recurrent cornea in conjunction with peak opacity mediated by CD4(+) T cells. Systemic administration of anti-IL-17 antibody resulted in a diminished severity of corneal opacity, neovascularization, and CD4(+) T cells infiltration compared to control. Anti-IL-17 treatment down-regulated the mRNA and protein levels of TNF-alpha. expression in recurrent corneas, and decreased HSV-specific DTH responses. Our results indicate that elevated IL-17 expression may be involved in the development of recurrent HSK. The likely mechanisms of action for IL-17 are through up-regulating TNF-alpha expression and promoting HSV-specific DTH responses. Thus, IL-17 might constitute a useful target for therapeutic intervention in recurrent HSK. (C) 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.