title: On the cytokine/chemokine network during Plasmodium vivax malaria: new insights to understand the disease.
abstract: The clinical outcome of malaria depends on the delicate balance between pro-inflammatory and immunomodulatory cytokine responses triggered during infection. Despite the numerous reports on characterization of plasma levels of cytokines/chemokines, there is no consensus on the profile of these mediators during blood stage malaria. The identification of acute phase biomarkers might contribute to a better understanding of the disease, allowing the use of more effective therapeutic approaches to prevent the progression towards severe disease. In the present study, the plasma levels of cytokines and chemokines and their association with parasitaemia and number of previous malaria episodes were evaluated in Plasmodium vivax-infected patients during acute and convalescence phase, as well as in healthy donors.
  
  
  
  Samples of plasma were obtained from peripheral blood samples from four different groups: P. vivax-infected, P. vivax-treated, endemic control and malaria-naïve control. The cytokine (IL-6, IL-10, IL-17, IL-27, TGF-β, IFN-γ and TNF) and chemokine (MCP-1/CCL2, IP-10/CXCL10 and RANTES/CCL5) plasma levels were measured by CBA or ELISA. The network analysis was performed using Spearman correlation coefficient.
  
  
  
  Plasmodium vivax infection induced a pro-inflammatory response driven by IL-6 and IL-17 associated with an immunomodulatory profile mediated by IL-10 and TGF-β. In addition, a reduction was observed of IFN-γ plasma levels in P. vivax group. A lower level of IL-27 was observed in endemic control group in comparison to malaria-naïve control group. No significant results were found for IL-12p40 and TNF. It was also observed that P. vivax infection promoted higher levels of MCP-1/CCL2 and IP-10/CXCL10 and lower levels of RANTES/CCL5. The plasma level of IL-10 was elevated in patients with high parasitaemia and with more than five previous malaria episodes. Furthermore, association profile between cytokine and chemokine levels were observed by correlation network analysis indicating signature patterns associated with different parasitaemia levels.
  
  
  
  The P. vivax infection triggers a balanced immune response mediated by IL-6 and MCP-1/CCL2, which is modulated by IL-10. In addition, the results indicated that IL-10 plasma levels are influenced by parasitaemia and number of previous malaria episodes.
authors.affiliation: Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Natália Satchiko
authors.initials: NS
authors.lastname: Hojo-Souza
authors.affiliation: Centro de Pesquisa em Medicina Tropical, Porto, Velho, Rondônia, Brazil.
authors.forename: Dhelio Batista
authors.initials: DB
authors.lastname: Pereira
authors.affiliation: Departamento de Ciência da Computação, Universidade Federal de São João del-Rei, São João del-Rei, Minas Gerais, Brazil.
authors.forename: Fernanda Sumika Hojo
authors.initials: FS
authors.lastname: de Souza
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil.
authors.forename: Tiago Antônio
authors.initials: TA
authors.lastname: de Oliveira Mendes
authors.affiliation: Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Mariana Santos
authors.initials: MS
authors.lastname: Cardoso
authors.affiliation: Centro de Pesquisa em Medicina Tropical, Porto, Velho, Rondônia, Brazil.
authors.forename: Mauro Shugiro
authors.initials: MS
authors.lastname: Tada
authors.affiliation: Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Graziela Maria
authors.initials: GM
authors.lastname: Zanini
authors.affiliation: Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Daniella Castanheira
authors.initials: DC
authors.lastname: Bartholomeu
authors.affiliation: Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Ricardo Toshio
authors.initials: RT
authors.lastname: Fujiwara
authors.affiliation: Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. llbueno@icb.ufmg.br.
authors.forename: Lilian Lacerda
authors.initials: LL
authors.lastname: Bueno
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007118:Immunoassay; D016780:Malaria, Vivax / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D055815:Young Adult
chemical_list: D016207:Cytokines
keywords: Chemokines; Cytokines; Malaria; Plasmodium vivax