Interleukin-10 reduces inflammation, endothelial dysfunction, and blood pressure in hypertensive pregnant rats

Abstract

Tinsley JH, South S, Chiasson VL, Mitchell BM. Interleukin-10 reduces inflammation, endothelial dysfunction, and blood pressure in hypertensive pregnant rats. Am J Physiol Regul Integr Comp Physiol 298: R713-R719, 2010. First published January 6, 2010 doi:10.1152/ajpregu.00712.2009.-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 IFN␥ 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 IFN␥, 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. preeclampsia; anti-inflammatory; hypertension; endothelin-1 PREECLAMPSIA (PE), DIAGNOSED as de novo hypertension and proteinuria during pregnancy, and other hypertensive disorders of pregnancy affect ϳ10% of pregnancies in the US and are responsible for 15-20% of maternal deaths worldwide (8). PE is associated with decreased fetal development and increased risk of future maternal heart disease. Although recent scientific findings have greatly aided in explaining the potential mechanisms involved in the development of PE, the exact causes remain unknown and effective treatments for PE remain elusive.Abnormal maternal immune system responses play a key role in the development of PE (10,13,31). A current theory is that women who develop PE have abnormal immunological responses to the fetus and placenta and that the hypertension and proteinuria represent clinical signs of a mild form of fetal rejection, while severe forms of PE result in spontaneous abortion and fetal demise. Consistent with this abnormal immunological response, cli...

Hypertension as an autoimmune and inflammatory disease

“…15 Evidence showing the effects of renal interstitial inflammation also comes from experimental studies that investigated the impact of anti-inflammatory cytokines, such as IL-10, on blood pressure. Tinsley et al 16 showed that the administration of intraperitoneal IL-10 normalized blood pressure and improved endothelial dysfunction in pregnant deoxycorticosterone acetate/saline-treated rats. More recently, Dhande et al 17 administered an AT2 receptor agonist to a monocyte cell line cell culture.…”

“…Exogenous IL-10 normalizes blood pressure and endothelial function in a rodent model of pregnancyinduced hypertension. 16 Several experimental studies demonstrated the importance of regulatory T cells in the prevention of immune cell infiltration and the consequent development of hypertension. 44,45 Despite compelling evidence for T-cell involvement as part of the adaptive immune system in the generation and propagation of hypertension, it remains to be determined why T cells infiltrate the kidney, vascular wall and central nervous system.…”

Interleukin-10, Mean Arterial Blood Pressure and Insulin Resistance in Normal Pregnancy

“…In a previous study, have been shown that administration of the IL-10 can normalize blood pressure in pregnancy-induced hypertensive rats (Tinsley et al, 2010). In other study antihuman IL-10 monoclonal antibody administration to baboons in early pregnancy, caused a significant increase in mean arterial pressure (Orangea et al, 2005).…”

Association of interleukin-10 gene promoter polymorphisms with recurrent pregnancy loss: a meta-analysis

“…Furthermore, increased IL-10 expression is associated with successful reproduction and IL-10 deficiency is associated with many adverse pregnancy outcomes such as PRL, preterm birth, and preeclampsia [11,[42][43][44]. Animal experimental studies also show that administration of recombinant IL-10 reverses or alleviates symptoms of many adverse pregnancy outcomes [45][46][47][48]. Polymorphic change in the human IL-10 gene promoter are thought to contribute to reduced IL-10 production and to the onset and severity of autoimmune, neoplastic, and infectious disorders such as systemic lupus erythematosus and Alzheimer's disease [49][50][51].…”