title: IL6 -174 G/C promoter polymorphism influences susceptibility to mucosal but not localized cutaneous leishmaniasis in Brazil.
abstract: BACKGROUND
  Mucosal leishmaniasis (ML) is associated with exaggerated tumor necrosis factor- alpha and interferon- gamma responses and tissue destruction. ML follows localized cutaneous leishmaniasis (CL) caused by Leishmania braziliensis infection. Interleukin (IL)-6 down-regulates T helper (Th) cell type 1 differentiation and drives Th2 cell differentiation. The IL6 -174 G/C polymorphism is associated with proinflammatory diseases and IL-6 regulation.
  
  
  METHODS
  The -174 G/C polymorphism was genotyped in population samples and families with CL and ML from Brazil. Genotype frequencies were compared among patients with ML, patients with CL, and 2 control groups by logistic regression and family-based association test (FBAT) analysis. IL-6 levels were measured in macrophages.
  
  
  RESULTS
  The C allele was more common in patients with ML than in patients with CL (odds ratio [OR], 2.55 [95% confidence interval {CI}, 1.32-4.91]; P=.005), than in patients who were leishmanin skin-test positive (OR, 2.23 [95% CI, 1.23-4.05]; P=.009), and than in neighborhood control subjects (OR, 2.47 [95% CI, 1.24-4.90]; P=.01). FBAT analysis confirmed an association between allele C and ML under both additive (z=4.295; P=.000017) and dominant (z=4.325; P=.000015) models. Significantly lower levels of IL-6 were measured in unstimulated macrophages from CC individuals than from GG individuals (P=.003) as well as after stimulation with soluble leishmania antigen (P=.009).
  
  
  CONCLUSIONS
  IL-6 may regulate type 1 proinflammatory responses, putting individuals with low macrophage IL-6 levels at increased risk for ML.
authors.affiliation: Servico de Imunologia, Hospital Universitario Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil.
authors.forename: Lea
authors.initials: L
authors.lastname: Castellucci
authors.forename: Eliane
authors.initials: E
authors.lastname: Menezes
authors.forename: Joyce
authors.initials: J
authors.lastname: Oliveira
authors.forename: Andrea
authors.initials: A
authors.lastname: Magalhaes
authors.forename: Luiz Henrique
authors.initials: LH
authors.lastname: Guimaraes
authors.forename: Marcus
authors.initials: M
authors.lastname: Lessa
authors.forename: Silvana
authors.initials: S
authors.lastname: Ribeiro
authors.forename: Jeancarlo
authors.initials: J
authors.lastname: Reale
authors.forename: Elza Ferreira
authors.initials: EF
authors.lastname: Noronha
authors.forename: Mary E
authors.initials: ME
authors.lastname: Wilson
authors.forename: Priya
authors.initials: P
authors.lastname: Duggal
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
authors.forename: Selma
authors.initials: S
authors.lastname: Jeronimo
authors.forename: Sarra E
authors.initials: SE
authors.lastname: Jamieson
authors.forename: Ashlee
authors.initials: A
authors.lastname: Bales
authors.forename: Jenefer M
authors.initials: JM
authors.lastname: Blackwell
authors.forename: Amelia Ribeiro
authors.initials: AR
authors.lastname: de Jesus
authors.forename: Edgar M
authors.initials: EM
authors.lastname: Carvalho
mesh_terms: D000328:Adult; D000818:Animals; D001938:Brazil / Q000453:epidemiology; D016022:Case-Control Studies; D005260:Female; D006798:Housing; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D007892:Leishmania braziliensis; D016773:Leishmaniasis, Cutaneous / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors
chemical_list: D015850:Interleukin-6