title: Melittin induces in vitro death of Leishmania (Leishmania) infantum by triggering the cellular innate immune response.
abstract: BACKGROUND
  Apis mellifera venom, which has already been recommended as an alternative anti-inflammatory treatment, may be also considered an important source of candidate molecules for biotechnological and biomedical uses, such as the treatment of parasitic diseases.
  
  
  METHODS
  Africanized honeybee venom from Apis mellifera was fractionated by RP-C18-HPLC and the obtained melittin was incubated with promastigotes and intracellular amastigotes of Leishmania (L.) infantum. Cytotoxicity to mice peritoneal macrophages was evaluated through mitochondrial oxidative activity. The production of anti- and pro-inflammatory cytokines, NO and H2O2 by macrophages was determined.
  
  
  RESULTS
  Promastigotes and intracellular amastigotes were susceptible to melittin (IC50 28.3 μg.mL(-1) and 1.4 μg.mL(-1), respectively), but also showed mammalian cell cytotoxicity with an IC50 value of 5.7 μg.mL(-1). Uninfected macrophages treated with melittin increased the production of IL-10, TNF-α, NO and H2O2. Infected melittin-treated macrophages increased IL-12 production, but decreased the levels of IL-10, TNF-α, NO and H2O2.
  
  
  CONCLUSIONS
  The results showed that melittin acts in vitro against promastigotes and intracellular amastigotes of Leishmania (L.) infantum. Furthermore, they can act indirectly on intracellular amastigotes through a macrophage immunomodulatory effect.
authors.affiliation: Graduate Program in Tropical Diseases, Botucatu Medical School, São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, SP Brazil.
authors.forename: Andreia Vieira
authors.initials: AV
authors.lastname: Pereira
authors.affiliation: Graduate Program in Tropical Diseases, Botucatu Medical School, São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, SP Brazil.
authors.forename: Gustavo
authors.initials: G
authors.lastname: de Barros
authors.affiliation: Department of Parasitology, Adolfo Lutz Institute, São Paulo, SP Brazil ; Laboratory of Protozoology, Institute for Tropical Medicine, University of São Paulo (USP), São Paulo, SP Brazil.
authors.forename: Erika Gracielle
authors.initials: EG
authors.lastname: Pinto
authors.affiliation: Department of Parasitology, Adolfo Lutz Institute, São Paulo, SP Brazil.
authors.forename: Andre Gustavo
authors.initials: AG
authors.lastname: Tempone
authors.affiliation: Department of Animal Production, School of Veterinary Medicine and Animal Husbandry, São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, SP Brazil ; Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP - Univ Estadual Paulista), Rua José Barbosa de Barros, 1780, 18610-307 Botucatu, SP Brazil.
authors.forename: Ricardo de Oliveira
authors.initials: Rde O
authors.lastname: Orsi
authors.affiliation: Graduate Program in Tropical Diseases, Botucatu Medical School, São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, SP Brazil ; Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP - Univ Estadual Paulista), Rua José Barbosa de Barros, 1780, 18610-307 Botucatu, SP Brazil.
authors.forename: Lucilene Delazari
authors.initials: LD
authors.lastname: Dos Santos
authors.affiliation: Graduate Program in Tropical Diseases, Botucatu Medical School, São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, SP Brazil ; Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP - Univ Estadual Paulista), Rua José Barbosa de Barros, 1780, 18610-307 Botucatu, SP Brazil.
authors.forename: Sueli
authors.initials: S
authors.lastname: Calvi
authors.affiliation: Graduate Program in Tropical Diseases, Botucatu Medical School, São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, SP Brazil ; Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP - Univ Estadual Paulista), Rua José Barbosa de Barros, 1780, 18610-307 Botucatu, SP Brazil.
authors.forename: Rui Seabra
authors.initials: RS
authors.lastname: Ferreira
authors.affiliation: Laboratory of Biochemistry and Biophysics, Butantan Institute, São Paulo, SP Brazil.
authors.forename: Daniel Carvalho
authors.identifier: 0000-0003-2406-0860
authors.initials: DC
authors.lastname: Pimenta
authors.affiliation: Graduate Program in Tropical Diseases, Botucatu Medical School, São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, SP Brazil ; Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP - Univ Estadual Paulista), Rua José Barbosa de Barros, 1780, 18610-307 Botucatu, SP Brazil.
authors.forename: Benedito
authors.initials: B
authors.lastname: Barraviera
keywords: Antiparasitic; Apis mellifera; Cytokines; Leishmania; Leishmaniasis; Melittin; Peptides; Toxins