title: Interleukin-4 deficiency induces mild preeclampsia in mice.
abstract: OBJECTIVE
  Inflammation is necessary for successful pregnancy; however, excessive inflammation plays a central role in the development of the pregnancy-specific hypertensive disorder preeclampsia. Numerous anti-inflammatory cytokines are decreased in women with preeclampsia but the role of individual cytokines in blood pressure regulation during pregnancy is unknown. Therefore, we examined whether the lack of the potent anti-inflammatory cytokine interleukin-4 (IL-4) would be sufficient to elicit a preeclampsia-like syndrome in mice, and when coupled with immune system activation that these symptoms would be further augmented.
  
  
  METHODS
  Measures of splenic immune cells, placental inflammation, blood pressure, endothelial function, and urinary protein excretion were performed in pregnant IL-4-deficient mice as well as in pregnant IL-4-deficient mice treated with the Toll-like receptor 3 agonist polyinosinic:polycytidylic (poly I:C).
  
  
  RESULTS
  Pregnant IL-4-deficient mice exhibited altered splenic immune cell subsets, increased levels of pro-inflammatory cytokines, placental inflammation, mild hypertension, endothelial dysfunction, and proteinuria compared to pregnant control mice. Compared to pregnant control mice treated with poly I:C which exhibit preeclampsia-like symptoms, poly I:C-treated pregnant IL-4-deficient mice exhibited a further increase in pro-inflammatory cytokine levels, which was associated with augmented SBP and endothelial dysfunction.
  
  
  CONCLUSIONS
  Collectively, these data show that the absence of IL-4 is sufficient to induce mild preeclampsia-like symptoms in mice due to excessive inflammation. Thus, the anti-inflammatory effects of IL-4 are important in preventing hypertension during pregnancy.
authors.affiliation: Department of Internal Medicine, Texas A&M Health Science Center/Scott & White Memorial Hospital, Temple, Texas 76504, USA.
authors.forename: Piyali
authors.initials: P
authors.lastname: Chatterjee
authors.forename: Shelley E
authors.initials: SE
authors.lastname: Kopriva
authors.forename: Valorie L
authors.initials: VL
authors.lastname: Chiasson
authors.forename: Kristina J
authors.initials: KJ
authors.lastname: Young
authors.forename: Richard P
authors.initials: RP
authors.lastname: Tobin
authors.forename: Karen
authors.initials: K
authors.lastname: Newell-Rogers
authors.forename: Brett M
authors.initials: BM
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006973:Hypertension / Q000150:complications; D007249:Inflammation / Q000097:blood / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood / Q000276:immunology; D015847:Interleukin-4 / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010920:Placenta / Q000276:immunology; D011225:Pre-Eclampsia / Q000097:blood* / Q000276:immunology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular; D011507:Proteinuria / Q000652:urine; D051196:Toll-Like Receptor 3 / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D015847:Interleukin-4