Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/7481
Title: Cytokine response signatures in disease progression and development of severe clinical outcomes for leptospirosis.
Authors: Reis, Eliana Almeida Gomes
Hagan, José Edward
Ribeiro, Guilherme de Sousa
Carvalho, Andréa Teixeira de
Martins Filho, Olindo Assis
Montgomery, Ruth R
Shaw, Albert C
Ko, Albert Icksang
Reis, Mitermayer Galvão dos
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Patologia e Biologia Molecular. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Patologia e Biologia Molecular. Salvador, BA, Brasil / Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, Connecticut, USA.
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Patologia e Biologia Molecular. Salvador, BA, Brasil / Federal University of Bahia. Institute of Collective Health. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil
Yale University School of Medicine. Yale University. Yale Department of Internal Medicine. New Haven, Connecticut, USA
Yale University School of Medicine. Yale University. Yale Department of Internal Medicine. New Haven, Connecticut, USA
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Patologia e Biologia Molecular. Salvador, BA, Brasil / Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, Connecticut, USA.
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Patologia e Biologia Molecular. Salvador, BA, Brasil / Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, Connecticut, USA.
Abstract: BACKGROUND: The role of the immune response in influencing leptospirosis clinical outcomes is not yet well understood. We hypothesized that acute-phase serum cytokine responses may play a role in disease progression, risk for death, and severe pulmonary hemorrhage syndrome (SPHS). METHODOLOGY/PRINCIPAL FINDINGS: We performed a case-control study design to compare cytokine profiles in patients with mild and severe forms of leptospirosis. Among patients hospitalized with severe disease, we compared those with fatal and nonfatal outcomes. During active outpatient and hospital-based surveillance we prospectively enrolled 172 patients, 23 with mild disease (outpatient) and 149 with severe leptospirosis (hospitalized). Circulating concentrations of pro- and anti-inflammatory cytokines at the time of patient presentation were measured using a multiplex bead array assay. Concentrations of IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, and TNF-α were significantly higher (P<0.05) in severe disease compared to mild disease. Among severe patients, levels of IL-6 (P<0.001), IL-8 (P = 0.0049) and IL-10 (P<0.001), were higher in fatal compared to non-fatal cases. High levels of IL-6 and IL-10 were independently associated (P<0.05) with case fatality after adjustment for age and days of symptoms. IL-6 levels were higher (P = 0.0519) among fatal cases who developed SPHS than among who did not. CONCLUSION/SIGNIFICANCE: This study shows that severe cases of leptospirosis are differentiated from mild disease by a "cytokine storm" process, and that IL-6 and IL-10 may play an immunopathogenic role in the development of life-threatening outcomes in human leptospirosis.
DeCS: Marcadores Biológicos/sangue
Citocinas/sangue
Leptospirose/imunologia
Leptospirose/patologia
Adolescente
Adulto
Estudos de Casos e Controles
Progressão da Doença
Feminino
Humanos
Leptospirose/mortalidade
Análise de Sobrevida
Meia-Idade
Masculino
Adulto Jovem
Issue Date: 2013
Publisher: Public Library of Science
Citation: REIS, E. A. G. et al. Cytokine response signatures in disease progression and development of severe clinical outcomes for leptospirosis. PLoS Neglected Tropical Diseases, v. 7, n. 9, p. e2457, 2013.
ISSN: 1935-2735
10.1371/journal.pntd.0002457
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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