A Murine Model Of Eczema Vaccinatum

RATIONALE: Eczema Vaccinatum (EV) is a complication of smallpox vaccination that affects patients with atopic dermatitis (AD). To understand how the vaccinia virus (VV) evades the host immune system and spread to induce disseminated satellite lesions in AD patients, we developed a murine model of EV. METHODS: BALB/c mice were shaved and epicutaneously (EC) sensitized with 100 microgram ovalbumin (OVA) or saline solution or were left unmanipulated. EC sensitized and unmanipulated skin sites were inoculated with 109 PFU of VV (Western Reserve) by scarification. Eight days later the number of satellite lesions, IgG1 virus-specific antibody level and viral tissue load were assessed. Th1 and Th2 cytokine production by splenocytes stimulated with VV were measured by ELISA. mRNA levels of cytokines and CRAMP (a cathelicidin shown to inhibit VV growth) in VV inoculated skin were assessed by quantitative RT-PCR. RESULTS: OVA EC sensitized mice exhibited a larger primary lesions, a higher number of satellite skin lesions and a higher serum level of IgG1-virus specific antibody. They also showed a significant increase in viral load in heart and kidney compared to unmanipulated mice. Their splenocytes had significantly decrease production of Th1 and Th2 cytokines in response to VV. Importantly, they showed a dramatic decrease in CRAMP mRNA expression at inoculated skin sites. CONCLUSIONS: Inoculation of VV into OVA sensitized skin sites may provide a good model for EV as it mirrors immunologic changes known to occur in patients with AD prone to viral infection.