Abstract
Abstract: :
Purpose: Dimethylfumarate (DMF) stimulates T helper–2–cytokines (interleukin (IL)–4, –5, –10) without affecting the T–helper–1–cytokine (IL–2, interferon (IFN)–γ)–response. Herein, the influence of systemic DMF–treatment on the secretion of T helper–cytokines and the development of HSV–1 stromal keratitis (HSK) was studied in mice. Methods: The right cornea of BALB/c mice was infected with HSV–1 (KOS). Groups of mice were treated intraperitoneally with: 1: vehicle for 28 days pre–infection; or 2: DMF for 28 days pre–infection; or 3: DMF for 14 days post–infection; or 4: DMF pre– and post–infection. The severity of HSK was analyzed clinically, and the corneal inflammatory cell infitration was studied histologically. Virus replication in the eyes was studied by a plaque–assay. The DTH–response and the serum neutralizing antibody–titers were investigated. IL–2, –4, –10 and IFN–γ – expression was analyzed in the corneas, spleens and regional lymph nodes by ELISA. Results: 72% of the mice from group 1 (n=14) developed severe HSK by day 14 p.i. DMF treatment reduced the development of keratitis in the groups 2 (35.2%, n=17), –3 (35%, n=20) and –4 (22%, n=19). The numbers of PMN, F4/80+ and CD3+ cells in the corneas were decreased in the DMF–treated mice; IL–4 and IL–10–secretion was increased in splenic lymphocytes and IL–4 was increased in the corneas. Virus–clearance from the eyes, the DTH and the neutralizing antibody–titers were not impaired. Conclusions: DMF induces the secretion of T helper–2–cytokines in the corneas and spleen of mice after corneal HSV–1 infection. This is associated with an improvement of HSK.
Keywords: herpes simplex virus • immunomodulation/immunoregulation • cornea: basic science