evp-4593 and Leishmaniasis--Cutaneous

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.

Topics: Animals; Antiprotozoal Agents; Drug Therapy, Combination; Interleukin-10; Interleukin-12; Interleukin-1beta; Leishmania mexicana; Leishmaniasis, Cutaneous; Macrophages, Peritoneal; Meglumine; Meglumine Antimoniate; Mice, Inbred BALB C; NF-kappa B; Organometallic Compounds; Phenyl Ethers; Quinazolines; Signal Transduction