Influence of dimethylfumarate on experimental HSV-1 necrotizing keratitis.
BACKGROUND
This study was performed to investigate the influence of fumaric acid esters on the course of herpes stromal keratitis (HSK).


METHODS
The corneas of BALB/c mice were inoculated with 105 plaque-forming units of herpes simplex virus 1 (HSV-1, KOS strain). Groups of mice were treated intraperitoneally with phosphate buffered saline (PBS) (control mice), or with dimethylfumarate (DMF) at 15 mg/kg of body weight dissolved in PBS daily for 28 days pre-infection and for 14 days post-infection. The course of HSV-1 keratitis was studied clinically. Corneal sections were examined for inflammatory cell infiltration. The numbers of CD3, GR-1, CD11b and F4/80-expressing cells infiltrating the corneas were analyzed by immunohistochemistry.


RESULTS
On day 14 after HSV infection, 72% of the mice in the control group had severe HSK. The development of HSK was reduced by DMF treatment in the DMF group (22%) (P=0.004). The total number of inflammatory cells and infiltration of polymorphonuclear-neutrophils (PMNs) were reduced in the corneas of DMF-treated mice. Compared to the PBS-treated mice, numbers of CD3, CD11b, GR-1 and F4/80-positive cells were reduced in the DMF group of mice.


CONCLUSIONS
The course of experimental herpes stromal keratitis can be improved with systemic fumaric acid ester treatment. The improvement of keratitis correlates with a reduced corneal infiltration of T cells and mononuclear cells.
Heiligenhaus
A
A
Ophtha-Lab, Department of Ophthalmology at St. Franziskus Hospital, Hohenzollernring 74, 48145 Muenster, Germany. arnd.heiligenhaus@uveitis-zentrum.de
Li
H
H
Wasmuth
S
S
Bauer
D
D
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D003319:Corneal Stroma / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D000069462:Dimethyl Fumarate; D005260:Female; D005650:Fumarates / Q000627:therapeutic use*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D007274:Injections, Intraperitoneal; D016849:Keratitis, Herpetic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology
D000943:Antigens, Differentiation; D039481:CD11b Antigen; D017252:CD3 Complex; D005650:Fumarates; C036763:monocyte-macrophage differentiation antigen; D000069462:Dimethyl Fumarate