Interferon-beta downregulates interferon-gamma-induced class II MHC molecule expression and morphological changes in primary cultures of human brain microvessel endothelial cells

J Neuroimmunol. 1995 Jul;60(1-2):63-73. doi: 10.1016/0165-5728(95)00054-6.


Regulation of class II MHC (Ia) antigen expression by interferons beta and gamma was studied in an in vitro model of the blood-brain barrier. Primary cultures of human brain microvessel endothelial cells were incubated with IFN-beta, gamma or a combination of the two cytokines and surface expression of class II MHC molecules was investigated with the immunogold silver staining technique and enzyme-linked immunosorbent assay. Treatment of monolayers with IFN-beta (100-6000 U/ml) failed to induce Class II MHC molecules. Co-incubation with IFN-gamma (100 U/ml), with or without pretreatment with IFN-beta, significantly inhibited the IFN-gamma-induced de novo expression in a concentration-dependent manner. Downregulation was less significant when incubation with both cytokines was preceded by 2-day treatment with IFN-gamma and was not observed in cultures incubated for an additional 4 days with IFN-gamma. Endothelial cells treated with IFN-gamma exhibited prominent morphological changes and frequent overlapping. These changes were not observed in the presence of either IFN-beta or both cytokines in the media. IFN-beta alone, or in combination with IFN-gamma, significantly inhibited the growth of endothelial cells, while only slight inhibition was observed with IFN-gamma. The results of these studies suggest that IFN-beta may function in modulating IFN-gamma-mediated immune responses in the human central nervous system at the level of the blood-brain barrier and this negative regulatory mechanism may be, at least in part, responsible for the recently reported beneficial effect of IFN-beta in relapsing-remitting multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cerebrovascular Circulation / drug effects*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Histocompatibility Antigens Class II / metabolism*
  • Humans
  • Immunohistochemistry
  • Interferon-beta / pharmacology*
  • Interferon-gamma / pharmacology*
  • Microcirculation / drug effects
  • Microscopy, Electron, Scanning


  • Histocompatibility Antigens Class II
  • Interferon-beta
  • Interferon-gamma