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

• TNF-α/IL-10 ratio is associated with the severity of hyperglycemia during gestation.
• Plasma TNF-α levels are higher in pregnant women with gestational diabetes.
• Plasma IL-10 levels are lower in pregnant women with type 2 diabetes.
• Placental TNF-α levels are higher in pregnant women with type 2 diabetes.
• TNF-α/IL-10 ratio during gestation should be considered as a key factor in clinical practice.

AimsTNF-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.MethodsOne 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.ResultsMaternal 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.ConclusionsAlterations 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.