title: Cotreatment with interleukin 4 and interleukin 10 modulates immune cells and prevents hypertension in pregnant mice.
abstract: 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(+)/γδ(+) 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.
authors.affiliation: Department of Internal Medicine, Texas A&M Health Science Center/Baylor Scott & White Health, Temple, Texas;
authors.forename: Piyali
authors.initials: P
authors.lastname: Chatterjee
authors.affiliation: Department of Internal Medicine, Texas A&M Health Science Center/Baylor Scott & White Health, Temple, Texas;
authors.forename: Valorie L
authors.initials: VL
authors.lastname: Chiasson
authors.affiliation: Department of Internal Medicine, Texas A&M Health Science Center/Baylor Scott & White Health, Temple, Texas;
authors.forename: Geetha
authors.initials: G
authors.lastname: Seerangan
authors.affiliation: Department of Surgery, Texas A&M Health Science Center/Baylor Scott & White Health, Temple, Texas.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Tobin
authors.affiliation: Department of Internal Medicine, Texas A&M Health Science Center/Baylor Scott & White Health, Temple, Texas;
authors.forename: Shelley E
authors.initials: SE
authors.lastname: Kopriva
authors.affiliation: Department of Surgery, Texas A&M Health Science Center/Baylor Scott & White Health, Temple, Texas.
authors.forename: M Karen
authors.initials: MK
authors.lastname: Newell-Rogers
authors.affiliation: Department of Internal Medicine, Texas A&M Health Science Center/Baylor Scott & White Health, Temple, Texas; bmitchell@tamhsc.edu.
authors.forename: Brett M
authors.initials: BM
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D005260:Female; D005313:Fetal Death / Q000517:prevention & control; D005865:Gestational Age; D007155:Immunologic Factors / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000097:blood; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D009336:Necrosis; D010920:Placenta / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D011070:Poly I-C; D011225:Pre-Eclampsia / Q000097:blood / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D011247:Pregnancy; D011507:Proteinuria / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D051196:Toll-Like Receptor 3 / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D016207:Cytokines; D007155:Immunologic Factors; D018836:Inflammation Mediators; D011994:Recombinant Proteins; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D016753:Interleukin-10; D015847:Interleukin-4; D011070:Poly I-C
keywords: blood pressure; endothelial dysfunction; hypertension; interleukin; polyinosinic polycytidylic acid; preeclampsia; proteinuria.