title: Increased interleukin-10 and interferon-γ levels in Plasmodium vivax malaria suggest a reciprocal regulation which is not altered by IL-10 gene promoter polymorphism.
abstract: BACKGROUND
  In human malaria, the naturally-acquired immune response can result in either the elimination of the parasite or a persistent response mediated by cytokines that leads to immunopathology. The cytokines are responsible for all the symptoms, pathological alterations and the outcome of the infection depends on the reciprocal regulation of the pro and anti-inflammatory cytokines. IL-10 and IFN-gamma are able to mediate this process and their production can be affected by single nucleotide polymorphisms (SNPs) on gene of these cytokines. In this study, the relationship between cytokine IL-10/IFN-gamma levels, parasitaemia, and their gene polymorphisms was examined and the participation of pro-inflammatory and regulatory balance during a natural immune response in Plasmodium vivax-infected individuals was observed.
  
  
  METHODS
  The serum levels of the cytokines IL-4, IL-12, IFN-gamma and IL-10 from 132 patients were evaluated by indirect enzyme-linked immunosorbent assays (ELISA). The polymorphism at position +874 of the IFN-gamma gene was identified by allele-specific polymerase chain reaction (ASO-PCR) method, and the polymorphism at position -1082 of the IL-10 gene was analysed by PCR-RFLP (PCR-Restriction Fragment Length Polymorphism).
  
  
  RESULTS
  The levels of a pro- (IFN-gamma) and an anti-inflammatory cytokine (IL-10) were significantly higher in P. vivax-infected individuals as compared to healthy controls. The IFN-gamma levels in primoinfected patients were significantly higher than in patients who had suffered only one and more than one previous episode. The mutant alleles of both IFN-gamma and IL-10 genes were more frequent than the wild allele. In the case of the IFNG+874 polymorphism (IFN-gamma) the frequencies of the mutant (A) and wild (T) alleles were 70.13% and 29.87%, respectively. Similar frequencies were recorded in IL-10-1082, with the mutant (A) allele returning a frequency of 70.78%, and the wild (G) allele a frequency of 29.22%. The frequencies of the alleles associated with reduced production of both IFN-gamma and IL-10 were high, but this effect was only observed in the production of IFN-gamma.
  
  
  CONCLUSIONS
  This study has shown evidence of reciprocal regulation of the levels of IL-10 and IFN-gamma cytokines in P. vivax malaria, which is not altered by the presence of polymorphism in the IL-10 gene.
authors.affiliation: Laboratório de Microbiologia e Imunologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Pará, CEP 66075-970, Brazil.
authors.forename: Tiago S
authors.initials: TS
authors.lastname: Medina
authors.forename: Sheyla P T
authors.initials: SP
authors.lastname: Costa
authors.forename: Maria D
authors.initials: MD
authors.lastname: Oliveira
authors.forename: Ana M
authors.initials: AM
authors.lastname: Ventura
authors.forename: José M
authors.initials: JM
authors.lastname: Souza
authors.forename: Tassia F
authors.initials: TF
authors.lastname: Gomes
authors.forename: Antonio C R
authors.initials: AC
authors.lastname: Vallinoto
authors.forename: Marinete M
authors.initials: MM
authors.lastname: Póvoa
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
authors.forename: Maristela G
authors.initials: MG
authors.lastname: Cunha
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001769:Blood / Q000276:immunology / Q000469:parasitology; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000097:blood* / Q000235:genetics; D007372:Interferons; D016753:Interleukin-10 / Q000097:blood* / Q000235:genetics; D016780:Malaria, Vivax / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018512:Parasitemia / Q000276:immunology; D010966:Plasmodium vivax / Q000276:immunology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D055815:Young Adult
chemical_list: C508609:IL10 protein, human; D016753:Interleukin-10; D007371:Interferon-gamma; D007372:Interferons