title: Changes in the TNF-alpha/IL-10 ratio in hyperglycemia-associated pregnancies.
abstract: OBJECTIVE
  TNF-α is a diabetogenic cytokine associated with adverse outcomes during pregnancy that can be counterbalanced by IL-10. We have investigated IL-10 and TNF-α balance at maternal and placental levels in hyperglycemia-associated pregnancies.
  
  
  METHODS
  One hundred and ninety-two pregnant women participated, which included normoglycemic women (ND) and women with mild gestational hyperglycemia (MGH), gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (DM2). Maternal plasma and placental tissue IL-10 and TNF-α levels were measured by ELISA and placental TNF-α was also immunolocalized.
  
  
  RESULTS
  Maternal plasma TNF-α levels were highest in GDM (p=0.0190), whereas TNF-α levels were highest in placental tissues in DM2 (p=0.0095). Immunohistochemistry also showed strong reactivity with anti-TNF-α antibody in the villous structures in the DM2 group. Conversely, IL-10 levels were lowest in maternal plasma of the DM2 group (p=0.0228). The TNF-α/IL-10 ratio in maternal plasma progressively increased with the severity of hyperglycemia (p<0.0001), being highest in placenta of the DM2 group (p=0.0150). In both, plasma and placenta, TNF-α/IL-10 ratio were correlated with mean maternal glycemia and HbA1c levels.
  
  
  CONCLUSIONS
  Alterations of placenta and serum TNF-α/IL-10 balance with predominance of TNF-α were correlated with the severity of hyperglycemia during gestation. This association may offer insight into the pathogenesis of gestational hyperglycemia and associated pregnancy outcomes.
authors: Post-graduate Program in Gynecology, Obstetrics and Mastology, Botucatu Medical School, São Paulo State University, São Paulo, Brazil. Electronic address: juscielemoreli@gmail.com.
authors: Jusciele B
authors: JB
authors: Moreli
authors: Post-graduate Program in Gynecology, Obstetrics and Mastology, Botucatu Medical School, São Paulo State University, São Paulo, Brazil; Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors: Simone
authors: S
authors: Corrêa-Silva
authors: Post-graduate Program in Gynecology, Obstetrics and Mastology, Botucatu Medical School, São Paulo State University, São Paulo, Brazil.
authors: Débora C
authors: DC
authors: Damasceno
authors: Post-graduate Program in Gynecology, Obstetrics and Mastology, Botucatu Medical School, São Paulo State University, São Paulo, Brazil.
authors: Yuri K
authors: YK
authors: Sinzato
authors: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors: Aline R
authors: AR
authors: Lorenzon-Ojea
authors: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors: Alexandre U
authors: AU
authors: Borbely
authors: Post-graduate Program in Gynecology, Obstetrics and Mastology, Botucatu Medical School, São Paulo State University, São Paulo, Brazil.
authors: Marilza V C
authors: MV
authors: Rudge
authors: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors: Estela
authors: E
authors: Bevilacqua
authors: Post-graduate Program in Gynecology, Obstetrics and Mastology, Botucatu Medical School, São Paulo State University, São Paulo, Brazil. Electronic address: calderon@fmb.unesp.br.
authors: Iracema M P
authors: IM
authors: Calderon
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000032:analysis / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology; D016640:Diabetes, Gestational / Q000097:blood / Q000453:epidemiology; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000453:epidemiology; D016753:Interleukin-10 / Q000032:analysis / Q000097:blood*; D010920:Placenta / Q000737:chemistry; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood* / Q000453:epidemiology; D011256:Pregnancy Outcome / Q000453:epidemiology; D011254:Pregnancy in Diabetics / Q000097:blood / Q000453:epidemiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000097:blood*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: Cytokines; Diabetes; Mild gestational hyperglycemia; Placenta