Therapeutic effects of nonerythropoietic erythropoietin analog ARA290 in experimental autoimmune encephalomyelitis rat.

Abstract

ARA290 is a nonerythropoietic analog of erythropoietin (EPO) containing 11 amino acids which provides the anti-inflammatory and neuroprotective effects of EPO without stimulating hematopoiesis. Here we studied the therapeutic effects of ARA290 in experimental autoimmune encephalomyelitis (EAE) Lewis rats. Therapeutic (from Day 7 to Day 18 or from Day 9 to Day 19) administration of ARA290 (35, 70 μg/kg, intra-peritoneal) to EAE rats once daily significantly reduced the severity and shortened the duration of clinical score, reduced the accumulation of inflammatory cells in EAE spinal cords and suppressed mRNA levels of interleukin-1β (IL-1β), IL-17, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), inducible nitric oxide synthase (iNOS), matrix metalloproteinase 9 (MMP9) and transcription factor T-bet in spinal cords of EAE rats. Furthermore, ARA290 treatment reduced the helper T cell number in lymph nodes and circulation in EAE. In vitro study showed that ARA290 dose-dependently inhibited antigen specific- and antigen non-specific-lymphocyte proliferation as well. In addition, ARA290 altered the cytokine milieu to favor the polarization of Th2 and regulatory T (Treg) cells but suppressed the polarization of Th1 and Th17 cells in EAE lymph nodes. In summary, our study here showed that ARA290 could alter T cell function to suppress inflammation to ameliorate EAE, suggesting that ARA290 may be a new therapeutic candidate for multiple sclerosis.

• Authors: Hong Chen, Bangwei Luo, Xiaofeng Yang, Jian Xiong, Zongwei Liu, Man Jiang, Rongchen Shi, Chuansheng Yan, Yuzhang Wu, Zhiren Zhang
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 268 Issue 1-2 Pg. 64-70 (Mar 15 2014) ISSN: 1872-8421 [Electronic] Netherlands
• PMID: 24518674 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Oligopeptides
• cibinetide

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Cell Differentiation (drug effects)
• Encephalomyelitis, Autoimmune, Experimental (immunology, pathology)
• Flow Cytometry
• Immunohistochemistry
• Oligopeptides (pharmacology)
• Rats
• Rats, Inbred Lew
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Spinal Cord (pathology)
• T-Lymphocytes, Helper-Inducer (cytology, drug effects)