title: 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: Institute of Immunology, Third Military Medical University of PLA, Gaotanyan Main Street 30, Chongqing 400038, People's Republic of China.
authors: Hong
authors: H
authors: Chen
authors: Institute of Immunology, Third Military Medical University of PLA, Gaotanyan Main Street 30, Chongqing 400038, People's Republic of China.
authors: Bangwei
authors: B
authors: Luo
authors: Institute of Immunology, Third Military Medical University of PLA, Gaotanyan Main Street 30, Chongqing 400038, People's Republic of China.
authors: Xiaofeng
authors: X
authors: Yang
authors: Institute of Immunology, Third Military Medical University of PLA, Gaotanyan Main Street 30, Chongqing 400038, People's Republic of China.
authors: Jian
authors: J
authors: Xiong
authors: Institute of Immunology, Third Military Medical University of PLA, Gaotanyan Main Street 30, Chongqing 400038, People's Republic of China.
authors: Zongwei
authors: Z
authors: Liu
authors: Institute of Immunology, Third Military Medical University of PLA, Gaotanyan Main Street 30, Chongqing 400038, People's Republic of China.
authors: Man
authors: M
authors: Jiang
authors: Institute of Immunology, Third Military Medical University of PLA, Gaotanyan Main Street 30, Chongqing 400038, People's Republic of China.
authors: Rongchen
authors: R
authors: Shi
authors: Institute of Immunology, Third Military Medical University of PLA, Gaotanyan Main Street 30, Chongqing 400038, People's Republic of China.
authors: Chuansheng
authors: C
authors: Yan
authors: Institute of Immunology, Third Military Medical University of PLA, Gaotanyan Main Street 30, Chongqing 400038, People's Republic of China. Electronic address: yuzhangwu@yahoo.com.cn.
authors: Yuzhang
authors: Y
authors: Wu
authors: Institute of Immunology, Third Military Medical University of PLA, Gaotanyan Main Street 30, Chongqing 400038, People's Republic of China. Electronic address: zhangzhiren@yahoo.com.
authors: Zhiren
authors: Z
authors: Zhang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry; D007150:Immunohistochemistry; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D009842:Oligopeptides; C576178:cibinetide
keywords: ARA290; Experimental autoimmune encephalomyelitis; Inflammation; Multiple sclerosis