title: Pravastatin modulates macrophage functions of Leishmania (L.) amazonensis-infected BALB/c mice.
abstract: The control of leishmaniases poses an important challenge due to the scarcity and toxicity of the pharmacological options available. We have previously shown that pravastatin significantly improves the course of the disease in Leishmania (L.) amazonensis-infected BALB/c mice. Since the drug caused no direct effect on the parasite, we decided to evaluate its immunomodulatory action in this experimental model. To evaluate the impact of pravastatin treatment, BALB/c mice infected or not with L. (L.) amazonensis were treated with pravastatin (20 mg/kg daily) or saline during 30 or 90 days and phagocytosis, hydrogen peroxide, nitric oxide and the tumor necrosis factor production by peritoneal macrophages were assessed. We showed that pravastatin increased the phagocytosis mediated by complement and immunoglobulin receptors (63.5 to 130.3; p=0.03, t test), but not that occurring via pattern recognition receptors, induced a rise of nitric oxide production by macrophages (2.1 μM to 12.9 μM; p=0.04, Mann-Whitney test), endowing these cells to better kill ingested leishmania organisms, caused no modification of the otherwise increased production of hydrogen peroxide by macrophages, and reduced the overproduction of tumor necrosis factor (166.6 pg/mL to 3.9 pg/mL; p=0.016, Mann-Whitney test), a major component of the exacerbated inflammation associated to leishmaniases. Our findings point to the potential usefulness of pravastatin as an adjunct to the treatment of leishmaniases, based on its powerful immunomodulatory effects and low toxicity.
authors: Laboratory of Cellular Immunology, Pathology, Faculty of Medicine, University of Brasilia, Brasilia 70.910-900, DF, Brazil. cscarlos@unb.br
authors: Carlos S
authors: CS
authors: Kückelhaus
authors: Selma A S
authors: SA
authors: Kückelhaus
authors: Carlos Eduardo
authors: CE
authors: Tosta
authors: Maria Imaculada
authors: MI
authors: Muniz-Junqueira
mesh_terms: D000818:Animals; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D007894:Leishmania mexicana / Q000187:drug effects* / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D017035:Pravastatin / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D017035:Pravastatin