Anti-Inflammatory Effect of Erythropoietin Therapy on Experimental Autoimmune Encephalomyelitis

Abstract

Previous studies report that erythropoietin (EPO) has a neuroprotective role in some neurodegenerative diseases, but the mechanisms are not completely elucidated. The aim of this study was to investigate whether EPO exerts neuroprotective role in experimental autoimmune encephalomyelitis (EAE) via the routes of anti-inflammation. We established an EAE mice model treated intraperitoneally with EPO at the dose of 5,000 IU/kg on schedule, and recorded the clinical score and weight fluctuation. The infiltration of inflammatory cells in the spinal cord of EAE mice was observed with hemotoxylin and eosin (HE) staining, and the levels of IL-10, IFN-γ, IL-17, and MHC-II in central nervous system (CNS)-infiltrating cells and peripheral mononuclear cells were detected by flow cytometry or ELISA. EPO therapy ameliorates clinical signs of EAE mice, inhibits the body weight loss, and decreases the infiltration of inflammatory cells in spinal cords. IL-17 and IFN-γ are reduced, while IL-10 is not increased significantly, in both CNS-infiltrating cells and peripheral mononuclear cells of EPO-treated EAE mice, as compared with EAE control group. EPO also reduces the expression of MHC-II on peripheral antigen presentation cells. Our results indicate that EPO exerts a beneficial role in EAE by inhibiting the levels of IL-17 and IFN-γ in peripheral splenic cells and CNS-infiltrating cells.

Erythropoietin exerts direct immunomodulatory effects on the cytokine production by activated human T-lymphocytes

“…This idea is consistent with experimental data indicating the ability Epo to attenuate the development of experimental autoimmune myocarditis [17,18] and experimental autoimmune encephalomyelitis [19,20]. Another rationale for the application of Epo in clinical settings would also be Epo-mediated up-regulation of erythropoiesis, which is usually negatively affected in patients with chronic inflammatory diseases [21].…”

Increased progression to kidney fibrosis after erythropoietin is used as a treatment for acute kidney injury

“…EPO may be anti-inflammatory (24, 40,74). This may occur indirectly because of rhEPO-induced modulation of cell death in the kidney after IR (1), but we did not find that rhEPO modulated acute or chronic inflammatory cell populations, or modulated the increased levels of TNF-␣ seen at 7 and 28 days post-IR.…”

A single intramuscular injection of rAAV‐mediated mutant erythropoietin protects against MPTP‐induced parkinsonism

“…This induces phosphorylation of Akt, resulting in dissociation of Bcl-2-associated death promoter (BAD) from the Bcl-2/Bcl-X complex and activation of components of the reperfusion injury signaling kinase (RISK) pathway to increase mitochondrial membrane potential and reduce oxidative stress (Kobayashi et al 2008;Miki et al 2009;Smith & Yellon 2011;Weishaupt et al 2004). Native Epo has also been shown to increase levels of anti-inflammatory interleukin-10 and attenuate inflammatory cytokines under pathological conditions (Chau et al 2011;Juul et al 2008;Lofrumento et al 2011;Sajja et al 2012;Zhang et al 2012). MPTP induces a robust inflammatory response and oxidative stress secondary to inhibition of complex I of the mitochondrial respiratory chain (Karunakaran et al 2007;Thomas et al 2012).…”