title: Combined interleukin-12 and topical chemotherapy for established Leishmaniasis drastically reduces tissue parasitism and relapses in susceptible mice.
abstract: 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)-gamma levels to low IL-4 and high IFN-gamma 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.
authors.affiliation: School of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: A P
authors.initials: AP
authors.lastname: Fernandes
authors.forename: F A
authors.initials: FA
authors.lastname: Carvalho
authors.forename: C A
authors.initials: CA
authors.lastname: Tavares
authors.forename: H C
authors.initials: HC
authors.lastname: Santiago
authors.forename: G A
authors.initials: GA
authors.lastname: Castro
authors.forename: W L
authors.initials: WL
authors.lastname: Tafuri
authors.forename: L A
authors.initials: LA
authors.lastname: Ferreira
authors.forename: R T
authors.initials: RT
authors.lastname: Gazzinelli
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D007371:Interferon-gamma / Q000032:analysis; D018664:Interleukin-12 / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000032:analysis; D018320:Leishmania major / Q000302:isolation & purification; D007896:Leishmaniasis / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D010303:Paromomycin / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000900:Anti-Bacterial Agents; D000981:Antiprotozoal Agents; D012333:RNA, Messenger; D011994:Recombinant Proteins; D018664:Interleukin-12; D015847:Interleukin-4; D010303:Paromomycin; D007371:Interferon-gamma