Cotreatment with interleukin 4 and interleukin 10 modulates immune cells and prevents hypertension in pregnant mice. Academic Article uri icon


  • BACKGROUND: Excessive maternal immune system activation plays a central role in the development of the hypertensive disorder of pregnancy preeclampsia (PE). The immunomodulatory cytokines interleukin 4 (IL-4) and interleukin 10 (IL-10) are dysregulated during PE; therefore we hypothesized that treatment with both recombinant IL-4 and IL-10 during pregnancy could prevent the development of PE in mice. METHODS: Using our mouse model of PE in which immune system activation is induced by the double-stranded RNA receptor agonist poly I:C, we gave daily injections of IL-4, IL-10, or both on days 13-17 of pregnancy. Mice were then killed on day 18. RESULTS: Poly I:C caused a significant increase in systolic blood pressure in pregnant (P-PIC) mice compared with vehicle-treated pregnant (P) mice. All 3 treatments significantly decreased blood pressure in P-PIC mice to P levels, ameliorated the endothelial dysfunction, and decreased placental TLR3 levels in P-PIC mice. However, only IL-4/IL-10 cotreatment prevented the proteinuria and increased incidence of fetal demise in P-PIC mice; IL-4 or IL-10 alone had no effect. Additionally, only IL-4/IL-10 cotreatment prevented the significant increase in CD3(+)/(+) T cells and CD11c(+) dendritic cells and significant decrease in CD11b(+)/CD14(-) suppressor monocytes, as well as completely prevented placental necrosis, in P-PIC mice. Importantly, IL-4/IL-10 cotreatment in P mice had no detrimental effects. CONCLUSIONS: Taken together, these data demonstrate that exogenous IL-4 and IL-10 administration concurrently during pregnancy can normalize immune cell subsets and prevent PE induced by maternal immune system activation.

published proceedings

  • Am J Hypertens

altmetric score

  • 1.5

author list (cited authors)

  • Chatterjee, P., Chiasson, V. L., Seerangan, G., Tobin, R. P., Kopriva, S. E., Newell-Rogers, M. K., & Mitchell, B. M.

citation count

  • 53

complete list of authors

  • Chatterjee, Piyali||Chiasson, Valorie L||Seerangan, Geetha||Tobin, Richard P||Kopriva, Shelley E||Newell-Rogers, M Karen||Mitchell, Brett M

publication date

  • January 2015