Altered production of brain-derived neurotrophic factor by peripheral blood immune cells in multiple sclerosis.
BACKGROUND
Within multiple sclerosis lesions, brain-derived neurotrophic factor is detected in neurons and immunocytes.


OBJECTIVE
To clarify brain-derived neurotrophic factor production by peripheral blood immunocytes and its relationship with clinical parameters in multiple sclerosis.


METHODS
Serum brain-derived neurotrophic factor levels were measured by conventional enzyme-linked immunosorbent assay while brain-derived neurotrophic factor production by immunocytes was determined by an in situ enzyme-linked immunosorbent assay in 74 multiple sclerosis patients, 32 healthy controls, and 86 patients with other neurological diseases. The tyrosine kinase receptor TrkB expression level in peripheral blood mononuclear cells was measured by real-time polymerase chain reaction.


RESULTS
Multiple sclerosis patients showed significantly higher serum brain-derived neurotrophic factor levels than healthy controls and patients with other neurological diseases. Multiple sclerosis patients with high brain-derived neurotrophic factor levels were younger, and showed fewer relapse numbers than those with low brain-derived neurotrophic factor levels. Brain-derived neurotrophic factor production by T cells increased with age in healthy controls, but not in multiple sclerosis patients. Interferon beta induced a significant increase in serum brain-derived neurotrophic factor levels. Brain-derived neurotrophic factor production from T cells and TrkB expression levels in peripheral blood mononuclear cells were significantly enhanced in interferon beta-treated multiple sclerosis patients compared with untreated ones.


CONCLUSIONS
A high brain-derived neurotrophic factor level is related to early mild disease in young multiple sclerosis patients. Interferon beta potentiates brain-derived neurotrophic factor production and brain-derived neurotrophic factor receptor expression in peripheral blood mononuclear cells, which may act beneficially.
Yoshimura
Satoshi
S
Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Ochi
Hirofumi
H
Isobe
Noriko
N
Matsushita
Takuya
T
Motomura
Kyoko
K
Matsuoka
Takeshi
T
Minohara
Motozumi
M
Kira
Jun-ichi
J
D000328:Adult; D000375:Aging / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020813:Receptor, trkB / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D012313:RNA; D016899:Interferon-beta; D020813:Receptor, trkB