EPO induced sustained immuno/inflammatory modulation by expanding peripheral Treg cell numbers and reducing Th17 positive cells.
Mice were immunized with MOG and received daily EPO treatment for 6 days (day1–6). a). EPO therapy for 6 days delayed onset of clinical neurologic signs in animals and reduced the magnitude of clinical deficit in EAE mice (•) compared to sham treated control (○) EAE mice (*, p<0.05). The clinical score was determined as the mean±SEM of 8 mice per group. Data represents the mean±SEM of 8 individual mice. b–c) DILNs were obtained from mice after 6 days treatment with either EPO or PBS. Cells were quantified for number of Tregs (CD4+Foxp3+) and Th17 by flow cytometry. Panel b shows that about 3.4% Treg cells were detectable in normal mouse inguinal lymph node (left). A reduced number (2.4%) of Treg cells was detected in sham treated EAE control mice nodes (middle), whereas EPO therapy induced a 2-fold increase in Foxp3+ Treg cells on day 16 compared to sham treatment (right). Panel c shows <0.2% of normal healthy lymph node cells stained positive for Th17 (left). Numbers of peripheral Th17 cells greatly increased on day 16 (15-fold) in EAE mice treated with PBS (middle, 3.2%). In marked contrast, EPO therapy (right) sharply reduced the number of peripheral Th17 cells in MOG-immunized animals.