Cotreatment with interleukin 4 and interleukin 10 modulates immune cells and prevents hypertension in pregnant mice.
Am J Hypertens
; 28(1): 135-42, 2015 Jan.
Article
en En
| MEDLINE
| ID: mdl-24906486
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 IC, 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 IC 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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Preeclampsia
/
Presión Sanguínea
/
Subgrupos de Linfocitos T
/
Interleucina-4
/
Interleucina-10
/
Factores Inmunológicos
/
Antihipertensivos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Am J Hypertens
Asunto de la revista:
ANGIOLOGIA
Año:
2015
Tipo del documento:
Article