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.
journal_name
Neurosci Lettjournal_title
Neuroscience lettersauthors
Noh MY,Cho KA,Kim H,Kim SM,Kim SHdoi
10.1016/j.neulet.2014.05.001subject
Has Abstractpub_date
2014-06-27 00:00:00pages
53-8eissn
0304-3940issn
1872-7972pii
S0304-3940(14)00365-6journal_volume
574pub_type
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