Open AccessThe Severity of Visceral Leishmaniasis Correlates with Elevated Levels of Serum IL-6, IL-27 and sCD14
Author(s) -
Priscila Lima dos Santos,
Fabrícia Alvisi de Oliveira,
Micheli Luize Barbosa Santos,
Luana Celina Seraphim Cunha,
Michelle Teles Barbosa Lino,
Michelle F. S. de Oliveira,
Manuela O. M. Bomfim,
Ângela Maria Silva,
Tatiana Rodrigues de Moura,
Amélia Ribeiro de Jesus,
Malcolm S. Duthie,
Steven G. Reed,
Roque Pacheco de Almeida
Publication year - 2016
Publication title -
plos neglected tropical diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.99
H-Index - 135
eISSN - 1935-2735
pISSN - 1935-2727
DOI - 10.1371/journal.pntd.0004375
Subject(s) - visceral leishmaniasis , immunology , immune system , leishmania infantum , leishmaniasis , cd14 , disease , asymptomatic , medicine , proinflammatory cytokine , biology , inflammation
Background Visceral leishmaniasis (VL) is a severe disease caused by infection with protozoa of the genus Leishmania . Classic VL is characterized by a systemic infection of phagocytic cells and an intense activation of the inflammatory response. It is unclear why 90% of infected individuals do not develop the disease while a minority develop the classical form. Furthermore, among those that develop disease, a small group progresses to more severe form that is unresponsive to treatment. The presence of inflammatory mediators in serum could theoretically help to control the infection. However, there is also a release of anti-inflammatory mediators that could interfere with the control of parasite multiplication. In this study, we took advantage of the spectrum of outcomes to test the hypothesis that the immune profile of individuals infected with Leishmania (L . ) infantum is associated with the development and severity of disease. Methodology/Principal Findings Sera from patients with confirmed diagnosis of VL were evaluated for the presence of numerous molecules, and levels compared with healthy control and asymptomatic infected individuals. Conclusions/Principal Findings Although differences were not observed in LPS levels, higher levels of sCD14 were detected in VL patients. Our data suggest that L . infantum may activate the inflammatory response via CD14, stimulating a generalized inflammatory response with production of several cytokines and soluble molecules, including IFN-γ, IL-27, IL-10, IL-6 and sCD14. These molecules were strongly associated with hepatosplenomegaly, neutropenia and thrombocytopenia. We also observed that IL-6 levels greater than 200 pg/ml were strongly associated with death. Together our data reinforce the close relationship of IFN-γ, IL-10, IL-6, TNF-α and IL-27 in the immune dynamics of VL and suggest the direct participation of sCD14 in the activation of the immune response against L . infantum .