Combined Interleukin-12 and Topical Chemotherapy for Established Leishmaniasis Drastically Reduces Tissue Parasitism and Relapses in Susceptible Mice

The efficacy of the association of paromomycin sulfate (PA) with recombinant (r) interleukin (IL)–12 was investigated by topical treatment of BALB/c mice infected with Leishmania major that displayed fully developed cutaneous lesions. Although healing was observed in PA-treated groups, lesions recurred in 100% of these animals 70 days after treatment. In contrast, lesions were absent in a high proportion of PA- and rIL-12–treated mice 120 days after treatment. The PA/rIL-12–treated mice had a switch in cytokine response, from high IL-4 and low interferon (IFN)–γ levels to low IL-4 and high IFN-γ levels, and reductions in parasite load, dissemination of parasites, and inflammation. Thus, the association of rIL-12 to topical chemotherapy for leishmaniasis may be an important strategy for increasing cure rates and decreasing the incidence of relapse