title: Erythropoietin modulates the immune-inflammatory response of a SOD1(G93A) transgenic mouse model of amyotrophic lateral sclerosis (ALS).
abstract: Temporal patterns of inflammatory cytokine levels reflect the immune-inflammatory role in pathogenic mechanisms of SOD1 animal model of Amyotrophic Lateral Sclerosis (ALS) and these cytokines have important roles in both toxic and protective functions depending on the stage of disease progression in ALS patients. Erythropoietin (EPO) has various neuroprotective effects, including the reduction of inflammation, the enhancement of survival signals, and the prevention of neuronal cell death. This study was undertaken to evaluate the temporal pattern of inflammatory cytokine levels induced by EPO treatment in the SOD1(G93A) mice model of ALS. We treated mice with 5 IU of EPO per gram of animal weight once every other week after the mice were 60 days old, and pro/anti-inflammatory cytokines were analyzed at 30, 60, 90, and 120 days of age. In untreated controls, pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β, CCL2 (MCP-1), CCL5 (RANTES), CXCL10 (IP-10), and IL-17A) were gradually increased with aging. In contrast, increment of anti-inflammatory cytokines (IL-4, IL-10, and TGF-β) showed the highest level at 90 days of age and their levels were remarkably faded until 120 days of age. EPO treatment, however, showed significantly decreased level of pro-inflammatory cytokines. And, up-regulated levels of anti-inflammatory cytokines with EPO were highly maintained until 120 days. In addition, the treatment of EPO delayed symptom onset, prolonged time of rotarod failure, and showed more preserved number of motoneurons. These findings suggest that EPO may be a potential therapeutic candidate having ability to modulate immune-inflammation in ALS.
authors.affiliation: Department of Neurology, Hanyang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Min Young
authors.initials: MY
authors.lastname: Noh
authors.affiliation: Department of Neurology, Hanyang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung Ah
authors.initials: KA
authors.lastname: Cho
authors.affiliation: Department of Neurology, Hanyang University College of Medicine, Seoul, Republic of Korea; Deparment of Laboratory Animal Center, Daugu-Gyeongbuk Medical Innovation Foudation, Republic of Korea.
authors.forename: Heejaung
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Neurology, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Neurology, Hanyang University College of Medicine, Seoul, Republic of Korea. Electronic address: kimsh1@hanyang.ac.kr.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death; D016207:Cytokines / Q000378:metabolism; D004921:Erythropoietin / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D015854:Up-Regulation
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; C000606290:SOD1 protein, human; D004921:Erythropoietin; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Amyotrophic lateral sclerosis; Erythropoietin; Inflammation; SOD1