Abstract 460: IL-33 Treatment Prevents Cyclosporine A-Induced Hypertension, Endothelial Dysfunction, and Vascular Remodeling in Mice Academic Article uri icon


  • The immunosuppressive drug cyclosporine A (CsA) causes systemic and renal vascular remodeling, endothelial dysfunction, and hypertension and this is associated with decreased anti-inflammatory regulatory T cells (Tregs). Myeloid-derived suppressor cells (MDSCs), a heterogeneous population of immature granulocytes, macrophages, and dendritic cells, play a central regulatory role in immune responses by inhibiting various pro-inflammatory innate and adaptive immune cells as well as stimulating Treg expansion. We hypothesized that CsA causes vascular remodeling, endothelial dysfunction, and hypertension in part by decreasing MDSCs and that augmentation of MDSCs in vivo with IL-33 treatment can prevent these effects. Daily treatment of male C57BL6/J mice for 1 week with CsA (50 mg/kg/day, ip) and IL-33 (0.5 ug/day, ip) prevented the CsA-induced decrease in splenic MDSC levels (Day 7 % of lymphocytes: Con=3.70.9, CsA=2.10.5*, CsA+IL-33=3.20.3; *p<0.05 vs. Con), increase in SBP (Day 7 SBP in mmHg: Con=943, CsA=1484*, CsA+IL-33=1003; *p<0.05 vs. Con), and decrease in maximal aortic endothelium-dependent relaxation responses (Con=782%, CsA=296%*, CsA+IL-33=742%; *p<0.05 vs. Con). Additionally, CsA treatment increased fibronectin protein levels in aortas and kidneys and caused renal intraglomerular mesangial expansion and congestion, all of which were ameliorated by co-treatment with IL-33. Together, these data suggest that the hypertension, endothelial dysfunction, and vascular remodeling caused by CsA is mediated in part by decreased MDSCs and that IL-33 treatment may have beneficial cardiovascular effects in CsA-treated patients.

published proceedings

  • Hypertension

author list (cited authors)

  • Chiasson, V. L., Manandhar, L., Roman, M. H., Bounds, K. R., & Mitchell, B. M.

citation count

  • 0

complete list of authors

  • Chiasson, Valorie L||Manandhar, Lochana||Roman, Marcos H||Bounds, Kelsey R||Mitchell, Brett M

publication date

  • January 2014