Cytokine response signatures in disease progression and development of severe clinical outcomes for leptospirosis.

dc.creatorReis, Eliana Almeida Gomes
dc.creatorHagan, José Edward
dc.creatorRibeiro, Guilherme de Sousa
dc.creatorCarvalho, Andréa Teixeira de
dc.creatorMartins Filho, Olindo Assis
dc.creatorMontgomery, Ruth R
dc.creatorShaw, Albert C
dc.creatorKo, Albert Icksang
dc.creatorReis, Mitermayer Galvão dos
dc.date2014-04-01T16:45:51Z
dc.date2014-04-01T16:45:51Z
dc.date2013
dc.date.accessioned2023-09-26T23:59:23Z
dc.date.available2023-09-26T23:59:23Z
dc.identifierREIS, 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.
dc.identifier1935-2735
dc.identifier10.1371/journal.pntd.0002457
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/7481
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8896285
dc.descriptionBACKGROUND: 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherPublic Library of Science
dc.rightsopen access
dc.subjectMarcadores Biológicos/sangue
dc.subjectCitocinas/sangue
dc.subjectLeptospirose/imunologia
dc.subjectLeptospirose/patologia
dc.subjectAdolescente
dc.subjectAdulto
dc.subjectEstudos de Casos e Controles
dc.subjectProgressão da Doença
dc.subjectFeminino
dc.subjectHumanos
dc.subjectLeptospirose/mortalidade
dc.subjectAnálise de Sobrevida
dc.subjectMeia-Idade
dc.subjectMasculino
dc.subjectAdulto Jovem
dc.titleCytokine response signatures in disease progression and development of severe clinical outcomes for leptospirosis.
dc.typeArticle


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