Suppression of cutaneous inflammation by intradermal gene delivery

Abstract

Biological effects of in vivo transfection of a potential anti-inflammatory gene, designated Sm16, cloned from the human parasite Schistosoma mansoni were analyzed in these studies. A single intradermal injection of a full-length cDNA of Sm16 resulted in the expression of Sm16 in the epidermis, dermis, skin migratory cells and skin-draining lymph nodes of mice for up to 7 days. Subsequently the anti-inflammatory effect of this gene expression was evaluated by inducing an inflammatory response in the skin of mice. These studies showed that Sm16 gene delivery resulted in a significant suppression of cutaneous inflammation as shown by a reduction in cutaneous edema, decrease in neutrophil infiltration, suppression of pro-inflammatory cytokine expression and down-regulation of ICAM-1 expression in the skin inflammatory site. Cells collected from the skin-draining lymph nodes showed reduced proliferation to mitogen. Multiple intradermal injection of Sm16 cDNA failed to induce any antibody response in mice for up to 8 weeks after initial injection. These findings suggest a potential for developing Sm16 gene delivery as a therapeutic agent for treating inflammatory skin disorders.