Format

Send to

Choose Destination
Exp Neurol. 2006 Mar;198(1):136-44. Epub 2006 Jan 19.

Amelioration of autoimmune neuroinflammation by recombinant human alpha-fetoprotein.

Author information

1
Laboratory of Neuroimmunology, Department of Neurology, the Agnes-Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, PO Box 12000, Jerusalem 91120, Israel.

Abstract

Alpha-fetoprotein (AFP) is a 65-kDa oncofetal glycoprotein found in fetal and maternal fluids during pregnancy. Clinical remissions during pregnancy have been observed in several autoimmune diseases, such as multiple sclerosis (MS), and have been attributed to the presence of pregnancy-associated natural immune-reactive substances, including AFP which can exert immunomodulatory effects on immune cells. In this study, we tested the effect of recombinant human AFP (rhAFP) isolated from transgenic goats, which contain the genomic DNA for hAFP, on experimental autoimmune encephalomyelitis (EAE), the animal model used for the study of MS. RhAFP treatment markedly improved the clinical manifestations of EAE, preventing central nervous system (CNS) inflammation and axonal degeneration. RhAFP exerted a broad immunomodulating activity, influencing the various populations of immune cells. T cells from treated mice had significantly reduced activity towards the encephalitogenic peptide of myelin oligodendrocyte glycoprotein (MOG), exhibiting less proliferation and reduced Th1 cytokine secretion. Moreover, AFP affected the humoral response, causing an inhibition in MOG-specific antibody production. The expression of CD11b, MHC class II and the chemokine receptor CCR5 was also down-regulated. This is the first study demonstrating reduced inflammation and axonal damage exerted by recombinant AFP. In light of our findings, rhAFP may serve as a potential candidate for treatment of MS and other autoimmune diseases.

PMID:
16423348
DOI:
10.1016/j.expneurol.2005.11.012
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center