engleski

Activity of azithromycin during leishmania infantum infection of human monocytes/macrophages

Visceral leishmaniasis (VL) is a chronic infectious disease caused by parasites of the genus Leishmania. Some success was achieved in the threatment of VL, but side effects and drug resistance are still serious problems. Leishmanias in humans live in macrophages as intracellular amastigotes, while in their sandfly vector live as extracellular promastigotes. As azithromycin (azalide antibiotic) concentrates in the tissues, especially in the macrophages we proposed that it could have a possible antileshmanial activity. The aim of this study was to investigate the activity of azithromycin against Leishmania infantum in infection of human monocytes. In addition, we wanted to detect possible immunomodulatory effects of tested drugs. For that purpose we isolated human monocytes from peripheral blood and infected them with logarithmic phase L. infantum promastigotes. Uninfected cells were used as controls. After incubation (24 hours) we added azithromycin or amphotericin B in different concentrations and after 3 days assessed the number of infected cells (per 100 cells), the number of amastigotes (per 100 cells) and the number of amastigotes per infected cell. We also did some proteinarray testing (Human Antibody Array III and 3.1, RayBiotech, Inc., USA) including 42 different inflammatory proteins from collected culture supernatants. We did not find any difference in the number of leishmania infected cells or in the number of amastigotes between azithromycin treated and control cells. In supernatants of uninfected monocytes azithromycin increased the level of IL-6 and decreased the levels of MIP-1β and TIMP-2, while amphotericin B decreased the levels of MIP-1β and TIMP-2. When monocytes infected with leishmania promastogotes were treated with azithromycin we found a decrease in the levels of MCP-1, TIMP-2 and MIP-1β , while amphotericin B treatment of Leishmania promastigotes influenced the production of IL-6 and decreased the production of MCP-1 and TIMP-2. Our results show that L. infantum is not susceptible to azithromycin treatment. However, there are some differences in immunomodulatory effects between azithromycin and amphotericin B. Further analyzes are necessary to find out which mechanisms are behind drug-resistance in leishmania infections.

leishmania infantum; azithromycin

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