title: The pentavalent antimonial therapy against experimental Leishmania amazonensis infection is more effective under the inhibition of the NF-κB pathway.
abstract: During Leishmania infection, host immune response is important to prevent the growth/survival of intracellular amastigotes. In this study, we evaluated in vitro and in vivo whether or not during Leishmania amazonensis infection, pentavalent antimonial treatment/therapy could be more effective under TNF-α inhibition. Both L. amazonensis-infected macrophages (in vitro model) and mice (in vivo model) were treated with a nuclear factor-κB (NF-κB) inhibitor and with Glucantime®, alone and in combined administrations. The in vitro amastigote counts, cytokines and nitrites' production were assessed after 48h incubation with the drugs. Paw lesion sizes and amastigote counts were also evaluated in vivo. Quantification of IL-1β from the infected tissue was performed. In vitro results show that when infected macrophages were incubated with QNZ+Glucantime®, a greater clearance was observed for the amastigotes' growth and this was related to greater nitrite production compared to the group that was only infected. In vivo results show that mice that received the combined treatment had their paw lesion sizes and amastigote nests inside the macrophages greatly diminished, correlating with increased IL-1β levels.
authors.affiliation: Laboratório de Biotecnologia Aplicada à Saúde, Fundação Oswaldo Cruz (Fiocruz Rondônia), BR-364, Km 3,5, 76812-245 Porto Velho, RO, Brazil; Programa de Pós-Graduação em Biologia Experimental (PGBioexp), Universidade Federal de Rondônia, BR-364, Km 9,5, 76801-059 Porto Velho, RO, Brazil.
authors.forename: Sharon Rose Aragão
authors.initials: SR
authors.lastname: Macedo
authors.affiliation: Laboratório de Biotecnologia Aplicada à Saúde, Fundação Oswaldo Cruz (Fiocruz Rondônia), BR-364, Km 3,5, 76812-245 Porto Velho, RO, Brazil; Programa de Pós-Graduação em Biologia Experimental (PGBioexp), Universidade Federal de Rondônia, BR-364, Km 9,5, 76801-059 Porto Velho, RO, Brazil.
authors.forename: Larissa Deadame
authors.initials: LD
authors.lastname: de Figueiredo Nicolete
authors.affiliation: Laboratório de Biotecnologia Aplicada à Saúde, Fundação Oswaldo Cruz (Fiocruz Rondônia), BR-364, Km 3,5, 76812-245 Porto Velho, RO, Brazil.
authors.forename: Amália Dos Santos
authors.initials: Ados S
authors.lastname: Ferreira
authors.affiliation: Laboratório de Biotecnologia Aplicada à Saúde, Fundação Oswaldo Cruz (Fiocruz Rondônia), BR-364, Km 3,5, 76812-245 Porto Velho, RO, Brazil; Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Amazônia Legal (Bionorte), BR-364, Km 5,5, 76815-800 Porto Velho, RO, Brazil.
authors.forename: Neuza Biguinati
authors.initials: NB
authors.lastname: de Barros
authors.affiliation: Laboratório de Biotecnologia Aplicada à Saúde, Fundação Oswaldo Cruz (Fiocruz Rondônia), BR-364, Km 3,5, 76812-245 Porto Velho, RO, Brazil; Programa de Pós-Graduação em Biologia Experimental (PGBioexp), Universidade Federal de Rondônia, BR-364, Km 9,5, 76801-059 Porto Velho, RO, Brazil; Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Amazônia Legal (Bionorte), BR-364, Km 5,5, 76815-800 Porto Velho, RO, Brazil. Electronic address: rnicolete@gmail.com.
authors.forename: Roberto
authors.initials: R
authors.lastname: Nicolete
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D007894:Leishmania mexicana; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology; D017737:Macrophages, Peritoneal / Q000276:immunology; D008536:Meglumine / Q000494:pharmacology / Q000627:therapeutic use*; D000077485:Meglumine Antimoniate; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000276:immunology; D009942:Organometallic Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D010647:Phenyl Ethers / Q000494:pharmacology / Q000627:therapeutic use*; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction
chemical_list: D000981:Antiprotozoal Agents; C562064:EVP 4593; C556062:IL10 protein, mouse; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D016328:NF-kappa B; D009942:Organometallic Compounds; D010647:Phenyl Ethers; D011799:Quinazolines; D016753:Interleukin-10; D018664:Interleukin-12; D008536:Meglumine; D000077485:Meglumine Antimoniate
keywords: Antimonial therapy; IL-1β; Immune response; Leishmania amazonensis; Nitric oxide; TNF-α inhibition