Modulatory effect of voriconazole on the production of proinflammatory cytokines in experimental cryptococcosis in mice with severe combined immunodeficiency

J Mycol Med. 2018 Mar;28(1):106-111. doi: 10.1016/j.mycmed.2017.11.008. Epub 2017 Dec 19.

Abstract

Cryptococcosis is a subacute or chronic disease. For many years, amphotericin B has been used in severe fungal infections. Voriconazole is a triazole with high bioavailability, a large distribution volume, and excellent penetration of the central nervous system (CNS). The objective of this study was to evaluate the production of pro-inflammatory cytokines in the lungs during an experimental infection caused by C. neoformans in murine model (SCID) that was treated with amphotericin B and voriconazole. After intravenous inoculation with 3.0×105 viable yeast cells, the animals were treated with amphotericin B and voriconazole. The daily treatments began 24hours after inoculation and lasted 15 days. We evaluated the survival curve and we measured the levels of TNF-α, IL-6 and IL-10. For all treatments, there was a significant increase in survival compared to the untreated group of animals and the group treated with voriconazole (maximum concentration). The levels of pro-inflammatory cytokines were significantly lower in the groups treated with voriconazole (maximum concentration) and amphotericin B (minimum concentration). Under the conditions studied, we can suggest by that the production of pro-inflammatory cytokines mediated by amphotericin B and voriconazole is dependent on the concentration administered.

Keywords: Amphotericin B; Cryptococcosis; Cryptococcus neoformans; Cytokines; SCID; Voriconazole.

MeSH terms

  • Amphotericin B / administration & dosage
  • Amphotericin B / therapeutic use
  • Animals
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / therapeutic use*
  • Cryptococcosis / drug therapy*
  • Cryptococcosis / microbiology
  • Cryptococcus neoformans / drug effects
  • Cryptococcus neoformans / immunology
  • Cytokines / drug effects*
  • Cytokines / immunology
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Inflammation / drug therapy
  • Inflammation / microbiology
  • Lung / immunology
  • Lung / microbiology
  • Lung Diseases, Fungal / immunology
  • Lung Diseases, Fungal / microbiology
  • Mice
  • Severe Combined Immunodeficiency / drug therapy
  • Severe Combined Immunodeficiency / immunology*
  • Severe Combined Immunodeficiency / microbiology
  • Voriconazole / administration & dosage
  • Voriconazole / therapeutic use*

Substances

  • Antifungal Agents
  • Cytokines
  • Amphotericin B
  • Voriconazole