Chloroquine is therapeutic in murine experimental model of paracoccidioidomycosis.
Chloroquine, due to its basic properties, has been shown to prevent the release of iron from holotransferrin, thereby interfering with normal iron metabolism in a variety of cell types. We have studied the effects of chloroquine on the evolution of experimental paracoccidioidomycosis by evaluating the viable fungal recovery from lung, liver and spleen from infected mice and H(2)O(2), NO production, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-10 levels and transferrin receptor (TfR) expression from uninfected and infected peritoneal macrophages. Chloroquine caused a significant decrease in the viable fungal recovery from all organs tested, during all periods of evaluation. Peritoneal macrophages from chloroquine-treated infected mice showed higher H(2)O(2) production and TfR expression, and decreased levels of NO, endogenous and stimulated-TNF-alpha, IL-6 and IL-10 during the three evaluated periods. However, despite its suppressor effects on the macrophage function, the chloroquine therapeutic effect upon murine paracoccidioidomycosis was probably due to its effect on iron metabolism, blocking iron uptake by cells, and consequently restricting iron to fungus growth and survival.
Dias-Melicio
Luciane Alarcão
LA
Department of Microbiology and Immunology, Biosciences Institute, São Paulo State University, São Paulo, Brazil. ladiasmelicio@ibb.unesp.br
Calvi
Sueli Aparecida
SA
Bordon
Ana Paula
AP
Golim
Marjorie A
MA
Peraçoli
Maria Terezinha Serrão
MT
Soares
Angela Maria Victoriano Campos
AM
D000818:Animals; D002738:Chloroquine / Q000494:pharmacology*; D004195:Disease Models, Animal; D006861:Hydrogen Peroxide / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis / Q000276:immunology; D010228:Paracoccidioides / Q000302:isolation & purification*; D010229:Paracoccidioidomycosis / Q000188:drug therapy* / Q000382:microbiology; D011990:Receptors, Transferrin / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D011990:Receptors, Transferrin; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002738:Chloroquine; D006861:Hydrogen Peroxide; D007501:Iron