Changes in the TNF-alpha/IL-10 ratio in hyperglycemia-associated pregnancies

Diabetes Res Clin Pract. 2015 Mar;107(3):362-9. doi: 10.1016/j.diabres.2015.01.005. Epub 2015 Jan 20.

Abstract

Aims: 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.

Keywords: Cytokines; Diabetes; Mild gestational hyperglycemia; Placenta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / analysis
  • Cross-Sectional Studies
  • Cytokines / analysis
  • Cytokines / blood
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes, Gestational / blood
  • Diabetes, Gestational / epidemiology
  • Female
  • Humans
  • Hyperglycemia / blood*
  • Hyperglycemia / epidemiology
  • Interleukin-10 / analysis
  • Interleukin-10 / blood*
  • Placenta / chemistry
  • Pregnancy
  • Pregnancy Complications / blood*
  • Pregnancy Complications / epidemiology
  • Pregnancy Outcome / epidemiology
  • Pregnancy in Diabetics / blood
  • Pregnancy in Diabetics / epidemiology
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / blood*
  • Young Adult

Substances

  • Blood Glucose
  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Interleukin-10