Abstract

A clioquinol (ICHQ)-containing Pluronic® F127 polymeric micelle system (ICHQ/Mic) was recently shown to be effective against Leishmania amazonensis infection in a murine model. In the present study, ICHQ/Mic was tested against L. infantum infection. BALB/c mice (n = 12 per group) were infected with L. infantum stationary promastigotes through subcutaneous injection and, 45 days after challenge, received saline or were treated via the subcutaneous route with empty micelles, ICHQ or ICHQ/Mic. In addition, animals were treated with miltefosine by the oral route, as a drug control. Half of the animals were euthanized 1 and 15 days after treatment, aiming to evaluate two endpoints after therapy, when parasitological and immunological parameters were investigated. Results showed that the treatment using miltefosine, ICHQ or ICHQ/Mic induced significantly higher anti-parasite IFN-γ, IL-12, GM-CSF, nitrite and IgG2a isotype antibody levels, which were associated with low IL-4 and IL-10 production. In addition, a higher frequency of IFN-γ and TNF-α-producing CD4+ and CD8+ T-cells was found in these animals. The parasite load was evaluated in distinct organs, and results showed that the treatment using miltefosine, ICHQ or ICHQ/Mic induced significant reductions in organic parasitism in the treated and infected mice. A comparison between the treatments suggested that ICHQ/Mic was the most effective in inducing a highly polarized Th1-type response, as well as reducing the parasite load in significant levels in the treated and infected animals. Data obtained 15 days after treatment suggested maintenance of the immunological and parasitological responses. In conclusion, ICHQ/Mic could be considered in future studies for the treatment of visceral leishmaniasis.

Highlights

  • Leishmaniases are diseases caused by parasitic protozoa belonging to more than 20 different Leishmania species [61]

  • ICHQ was incorporated in a Poloxamer 407-based micelle system, and the composition was evaluated for the treatment of L. infantum-infected BALB/c mice

  • Performing the evaluations one day after treatment, results showed that spleen cells of the miltefosine, ICHQ or ICHQ/Mic-treated mice produced significantly higher IFN-c, IL-12 and GM-CSF levels, which were associated with low IL-4 and IL-10 production

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Summary

Introduction

Leishmaniases are diseases caused by parasitic protozoa belonging to more than 20 different Leishmania species [61]. Distinct clinical manifestations of this disease complex are found in infected mammalian hosts, ranging from self-curing cutaneous lesions to life-threatening visceral disease [60]. Visceral leishmaniasis (VL) is caused by Leishmania donovani species in Asia and Africa, and by L. infantum in the Mediterranean Basin, Middle East and the Americas. Acute disease, which is characterized by several symptoms, such as fever, anemia, weight loss and fatigue, can be fatal if left untreated [12, 28]. About 0.2–0.4 million VL cases occur each year, of which the majority are reported in India, where the disease is an important public health problem [52]. In the Americas, Brazil accounts for about 90% of the VL cases recorded annually [60]

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