title: Circulating cytokines and chemokines associated with plasma leakage and hepatic dysfunction in Brazilian children with dengue fever.
abstract: Dengue fever is usually a benign acute viral infection transmitted by arthropods but may evolve to severe clinical manifestations such as coagulation and/or hemodynamic disorders, caused mainly by an increase of vascular permeability. Deregulated circulating immunological factors have been associated with severity. In Brazil severe cases appeared in children only recently and we evaluated the profile of cytokine/chemokine kinetics in 134 hospitalized young patients during the epidemic in Rio de Janeiro in 2008. Inflammatory cytokines TNF and IFNγ were found elevated during the acute phase in children as well as the anti-inflammatory IL10 and chemokines MIF and CXCL10/IP10, all last three persisting longer during the recovery phase. Severe disease fitting the dengue hemorrhagic fever pattern (WHO, 1997) was associated with higher IL10 and CXCL10/IP10 circulating levels (peak levels at seven days with P<0.01 and P<0.001 respectively as compared to DF). These factors were higher in patients pulmonary effusion or ascites (P<0.05 for IL10 and P<0.01 for CXCL10/IP10). Both factors were also associated with liver changes such as AST increase correlated with CXCL10/IP10 (r=0.4300 with P<0.0001) and patients presenting painful hepatomegaly showed higher circulating levels of IL10 (P<0.01, at 7-9 days) and of CXCL10/IP10 (P<0.05, 4-6 days and P<0.001, 7-9 days) when compared to patients without apparent liver alterations. Most cases presented a history of prior infection (93%). This is the first study demonstrating cytokine and chemokine association with severity during dengue fever in Brazilian children. IL10 and CXCL10/IP10 play a role in the disease severity associated with induction of vascular leakage and a novel association with changes in liver dysfunction.
authors.affiliation: Disciplina de Doenças Infecciosas e Parasitárias, Hospital Universitário Antônio Pedro, Universidade, Federal Fluminense, Niterói, RJ, Brazil.
authors.forename: Ralph Antonio Xavier
authors.initials: RA
authors.lastname: Ferreira
authors.affiliation: Disciplina de Doenças Infecciosas e Parasitárias, Hospital Universitário Antônio Pedro, Universidade, Federal Fluminense, Niterói, RJ, Brazil.
authors.forename: Solange Artimos
authors.initials: SA
authors.lastname: de Oliveira
authors.affiliation: Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Gandini
authors.affiliation: Disciplina de Doenças Infecciosas e Parasitárias, Hospital Universitário Antônio Pedro, Universidade, Federal Fluminense, Niterói, RJ, Brazil.
authors.forename: Laura da Cunha
authors.initials: Lda C
authors.lastname: Ferreira
authors.affiliation: Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Gladys
authors.initials: G
authors.lastname: Correa
authors.affiliation: Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Fernanda Mattos
authors.initials: FM
authors.lastname: Abiraude
authors.affiliation: Setor de Pediatria, Hospital Municipal Jesus, Secretaria Municipal de Saúde do Rio de Janeiro, RJ, Brazil.
authors.forename: Mariana Mancebo
authors.initials: MM
authors.lastname: Reid
authors.affiliation: Programa de Computação Científica (PROCC), FIOCRUZ, Rio de Janeiro, RJ, Brazil.
authors.forename: Oswaldo Gonçalves
authors.initials: OG
authors.lastname: Cruz
authors.affiliation: Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil. Electronic address: claire@ioc.fiocruz.br.
authors.forename: Claire Fernandes
authors.initials: CF
authors.lastname: Kubelka
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000410:Alanine Transaminase / Q000378:metabolism; D001201:Ascites / Q000209:etiology / Q000276:immunology; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001938:Brazil / Q000453:epidemiology; D002199:Capillary Permeability / Q000276:immunology*; D054357:Chemokine CXCL10 / Q000276:immunology; D018925:Chemokines / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016207:Cytokines / Q000276:immunology; D003715:Dengue / Q000150:complications / Q000453:epidemiology / Q000276:immunology; D058872:Epidemics; D005260:Female; D006529:Hepatomegaly / Q000209:etiology / Q000276:immunology; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D019746:Intramolecular Oxidoreductases / Q000276:immunology; D008107:Liver Diseases / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000276:immunology; D008297:Male; D010996:Pleural Effusion / Q000209:etiology / Q000276:immunology; D012189:Retrospective Studies; D019595:Severe Dengue / Q000150:complications / Q000453:epidemiology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D018925:Chemokines; D016207:Cytokines; D018793:Interleukin-13; D008263:Macrophage Migration-Inhibitory Factors; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
keywords: Brazil; Chemokines; Children; Cytokines; Dengue; Liver