Interleukin-10 reduces inflammation, endothelial dysfunction, and blood pressure in hypertensive pregnant rats.
Hypertensive disorders of pregnancy are characterized by systemic and placental inflammation; however, treatment for these conditions has remained elusive. We tested whether administration of the anti-inflammatory cytokine interleukin-10 (IL-10) during pregnancy would attenuate the hypertension, endothelial dysfunction, proteinuria, and inflammation seen in pregnant DOCA/saline-treated (PDS) rats. Normal pregnant (NP) rats and PDS were given daily intraperitoneal injections of recombinant IL-10 from gestational day 13 until death on day 20. Systolic blood pressure, aortic endothelium-dependent relaxation responses, and urinary protein excretion were measured on days 13 and 20 of gestation. Fetal number and development, plasma endothelin-1 levels, serum and placental levels of IFNgamma and IL-10, and aortic and placental levels of platelet endothelial cell adhesion molecule (PECAM) were assessed on gestational day 20. Systolic blood pressure, aortic endothelial dysfunction, and urinary protein excretion were significantly increased at gestational day 13 in PDS rats. However, all of these were restored to NP levels following IL-10 treatment in PDS rats. IL-10 treatment also significantly increased the number of pups per litter in PDS rats and did not further affect fetal development. The beneficial effects of IL-10 in PDS rats were likely mediated by the decreased plasma levels of endothelin-1, decreased levels of circulating and placental IFNgamma, as well as decreased aortic and placental expression of PECAM. These data demonstrate that exogenous IL-10 can normalize blood pressure and endothelial function in pregnancy-induced hypertensive rats and may be beneficial in women with hypertensive disorders of pregnancy.
Tinsley
John H
JH
Department of Internal Medicine, Division of Nephrology and Hypertension, Texas A&M Health Science Center, College of Medicine/Scott & White Memorial Hospital, Temple, TX 76504, USA.
South
Sanique
S
Chiasson
Valorie L
VL
Mitchell
Brett M
BM
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects* / Q000276:immunology; D000013:Congenital Abnormalities; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D046110:Hypertension, Pregnancy-Induced / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood / Q000494:pharmacology*; D008098:Litter Size / Q000187:drug effects; D008297:Male; D010920:Placenta / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011225:Pre-Eclampsia / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D011247:Pregnancy; D011507:Proteinuria / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
D019332:Endothelin-1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011994:Recombinant Proteins; D016753:Interleukin-10; D007371:Interferon-gamma