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Serum enkephalin levels correlate with EAE disease severity
Author(s) -
Ludwig Michael D.,
Zagon Ian S.,
McLaughlin Patricia J
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.745.3
Subject(s) - experimental autoimmune encephalomyelitis , multiple sclerosis , enkephalin , medicine , immunology , encephalomyelitis , spleen , endocrinology , immune system , opioid , receptor
Multiple sclerosis, and the animal model experimental autoimmune encephalomyelitis (EAE), are characterized by elevated immune cell replication. The endogenous peptide, opioid growth factor (OGF), chemically termed [Met 5 ]‐enkephalin has been shown to inhibit proliferation of activated T and B cells in vitro , and to reduce the number of T and B cells in peripheral tissues spleen, nodes) and CNS (spinal cord) following EAE immunization. Systemic OGF injection of mice with chronic EAE or relapse‐remitting EAE results in diminishment of clinical disease, reductions in activated astrocytes, and fewer relapses. The hypothesis of this research is that serum levels of OGF decline during the course of EAE, and that treatment with exogenous OGF is associated with severity of disease. The chronic mouse model of MS (Ch‐EAE) was established, with one group of mice receiving daily OGF injections beginning at the time of clinical disease onset. Clinical behavior was monitored daily; locomotor activity and thermal sensitivity were measured periodically. Blood samples were collected and enkephalin (OGF) levels measured by ELISA (MyBiosource). EAE disease onset occurred on day 9 post immunization when the mean clinical score was 1.5. Peak disease scores for saline‐injected EAE mice reached a mean of 5.7 on day 18, in comparison to a peak clinical score of 2.5 for EAE‐mice receiving OGF. Serum OGF levels in non‐diseased mice were approximately 149 pg/ml, whereas EAE mice had serum OGF levels that ranged between 8 and 128 pg/ml, suggesting that EAE corresponded to a decrease in enkephalins. Following exogenous OGF therapy, serum levels increased; higher serum OGF levels were related to reduce disease severity, as well as changes in open field behavior and hot‐plate sensitivity. These data suggest that there is a dysregulation of endogenous OGF in the disease state and that treatment with exogenous OGF restores serum OGF levels to normal. Moreover, the non‐invasive tracking of serum OGF may be useful as a marker for disease progression and response to therapy. Support or Funding Information Supported in part by the generous gifts from The Paul K. and Anna E. Shockey Family Foundation