Interferon-beta therapy up-regulates BDNF secretion from PBMCs of MS patients through a CD40-dependent mechanism.
We had reported that immune cells from relapsing remitting multiple sclerosis (RR-MS) patients secrete low levels of BDNF and that there is a defective regulation of its secretion via DC40. We now studied the effect of interferon-beta (IFN-beta1) on the secretion and regulation of BDNF from immune cells in patients with RR-MS. The PBMCs of IFN-beta1a treated RR-MS patients secreted higher BDNF levels vs. untreated patients. Anti CD40 mAb stimulation of PBMCs of IFN-beta1a treated patients upregulated the BDNF levels. There was no significant effect of CD40 stimulation on PBMCs of untreated patients. CD40(+) expression on CD14(+) cells was higher in IFN-beta treated patients vs. untreated patients. In vitro treatment with IFN-beta1a of PBMCs from healthy controls and untreated patients led to a significant increase in CD40 expression on CD14(+) cells in both groups. The addition of IFN-beta1a to CD40 stimulated PBMCs of untreated patients restored the up regulatory effect of CD40 stimulation on BDNF levels. Therefore, reduced BDNF secretion from PBMCs and defective regulation effect of CD40 stimulation on BDNF levels in untreated RR-MS are reversible by therapy with IFN-beta1a.
Azoulay
David
D
Tel Aviv University, Israel.
Mausner-Fainberg
Karin
K
Urshansky
Nataly
N
Fahoum
Firas
F
Karni
Arnon
A
D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects* / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
D019208:Brain-Derived Neurotrophic Factor; D019013:CD40 Antigens; D007155:Immunologic Factors; D016899:Interferon-beta