Anti-parasite therapy drives changes in human visceral leishmaniasis-associated inflammatory balance.
Théo Araujo-SantosBruno B AndradeLeonardo Gil-SantanaNívea F LuzPriscila L Dos SantosFabrícia A de OliveiraMeirielly Lima AlmeidaRoseane Nunes de Santana CamposPatrícia T BozzaRoque P AlmeidaValéria Matos BorgesPublished in: Scientific reports (2017)
Visceral leishmaniasis (VL) remains a major public health problem worldwide. Cytokine balance is thought to play a critical role in the development of this disease. Here, we perform a prospective exploratory study addressing whether simultaneous assessment of circulating levels of different lipid mediators and cytokines could highlight specific pathways involved with VL pathogenesis. VL patients displayed substantial increases in serum levels of Prostaglandin F2α (PGF2α), Leukotriene B4 (LTB4), Resolvin D1 (RvD1), IL-1β, IL-6, IL-8, IL-10, IL-12p70 and TNF-α compared with uninfected endemic control group, while exhibiting decreased levels of TGF-β1. Hierarchical cluster analysis of the prospective changes in the expression level of theses parameters upon anti-Leishmania treatment initiation revealed that the inflammatory profile observed in active disease gradually changed over time and was generally reversed at day 30 of therapy. Furthermore, not only the individual concentrations of most of the inflammatory biomarkers changed upon treatment, but the correlations between those and several biochemical parameters used to characterize VL disease activity were also modified over time. These results demonstrate that an inflammatory imbalance hallmarks active VL disease and open perspective for manipulation of these pathways in future studies examining a potential host-directed therapy against VL.
Keyphrases
- disease activity
- public health
- rheumatoid arthritis
- oxidative stress
- systemic lupus erythematosus
- end stage renal disease
- poor prognosis
- ankylosing spondylitis
- minimally invasive
- newly diagnosed
- juvenile idiopathic arthritis
- bone marrow
- hiv infected
- stem cells
- current status
- prognostic factors
- risk assessment
- climate change
- single cell
- replacement therapy
- human health
- induced pluripotent stem cells
- life cycle