title: The Severity of Visceral Leishmaniasis Correlates with Elevated Levels of Serum IL-6, IL-27 and sCD14.
abstract: 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.
  
  
  RESULTS
  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.
  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.
authors.affiliation: Laboratório de Biologia Molecular, Hospital Universitário, Universidade Federal de Sergipe, Aracaju, Brazil.
authors.forename: Priscila L
authors.initials: PL
authors.lastname: Dos Santos
authors.affiliation: Laboratório de Biologia Molecular, Hospital Universitário, Universidade Federal de Sergipe, Aracaju, Brazil.
authors.forename: Fabrícia A
authors.initials: FA
authors.lastname: de Oliveira
authors.affiliation: Laboratório de Biologia Molecular, Hospital Universitário, Universidade Federal de Sergipe, Aracaju, Brazil.
authors.forename: Micheli Luize B
authors.initials: ML
authors.lastname: Santos
authors.affiliation: Laboratório de Biologia Molecular, Hospital Universitário, Universidade Federal de Sergipe, Aracaju, Brazil.
authors.forename: Luana Celina S
authors.initials: LC
authors.lastname: Cunha
authors.affiliation: Laboratório de Biologia Molecular, Hospital Universitário, Universidade Federal de Sergipe, Aracaju, Brazil.
authors.forename: Michelle T B
authors.initials: MT
authors.lastname: Lino
authors.affiliation: Laboratório de Biologia Molecular, Hospital Universitário, Universidade Federal de Sergipe, Aracaju, Brazil.
authors.forename: Michelle F S
authors.initials: MF
authors.lastname: de Oliveira
authors.affiliation: Laboratório de Biologia Molecular, Hospital Universitário, Universidade Federal de Sergipe, Aracaju, Brazil.
authors.forename: Manuela O M
authors.initials: MO
authors.lastname: Bomfim
authors.affiliation: Laboratório de Biologia Molecular, Hospital Universitário, Universidade Federal de Sergipe, Aracaju, Brazil.
authors.forename: Angela Maria
authors.initials: AM
authors.lastname: Silva
authors.affiliation: Laboratório de Biologia Molecular, Hospital Universitário, Universidade Federal de Sergipe, Aracaju, Brazil.
authors.forename: Tatiana R
authors.initials: TR
authors.lastname: de Moura
authors.affiliation: Laboratório de Biologia Molecular, Hospital Universitário, Universidade Federal de Sergipe, Aracaju, Brazil.|Programa de Pós Graduação em Ciências da Saúde, Universidade Federal de Sergipe, Aracaju, Brazil.|Instituto de Investigação em Imunologia, São Paulo, Brazil.
authors.forename: Amélia R
authors.initials: AR
authors.lastname: de Jesus
authors.affiliation: Infectious Diseases Research Institute (IDRI), Seattle, Washington, United States of America.
authors.forename: Malcolm S
authors.initials: MS
authors.lastname: Duthie
authors.affiliation: Infectious Diseases Research Institute (IDRI), Seattle, Washington, United States of America.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.affiliation: Laboratório de Biologia Molecular, Hospital Universitário, Universidade Federal de Sergipe, Aracaju, Brazil.|Programa de Pós Graduação em Ciências da Saúde, Universidade Federal de Sergipe, Aracaju, Brazil.|Instituto de Investigação em Imunologia, São Paulo, Brazil.
authors.forename: Roque P
authors.initials: RP
authors.lastname: de Almeida
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007223:Infant; D064094:Interleukin-27 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D018314:Leishmania infantum / Q000502:physiology; D007898:Leishmaniasis, Visceral / Q000097:blood* / Q000469:parasitology / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D064094:Interleukin-27; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors
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