Multiple sclerosis: involvement of interferons in lesion pathogenesis.
To investigate a possible role of interferons (IFNs) in lesion pathogenesis, central nervous system tissue from multiple sclerosis patients and control subjects was stained by immunocytochemical techniques in combination with monoclonal antibodies or polyclonal antisera for the demonstration of IFN-alpha, IFN-beta, and IFN-gamma. The results were correlated to lesion activity, to the presence of class I and class II major histocompatibility antigen-positive astrocytes, and to the composition of cellular infiltrates. IFNs were detectable in active but not in inactive chronic multiple sclerosis lesions. In acute multiple sclerosis plaques, all three types of IFN were widely distributed on glial elements and infiltrating cells. In active chronic multiple sclerosis, labeling of cells for IFN-alpha, IFN-beta, and IFN-gamma was most pronounced at the lesion edge and displayed distinct distribution patterns. Overall, IFN-gamma was more common than IFN-alpha and IFN-beta and was predominantly found on astrocytes. IFN-alpha was detectable mainly on macrophages. Distribution of IFN-beta partially overlapped with that of IFN-gamma and IFN-alpha, in that it was present on some astrocytes and on some macrophages. IFNs were rare in normal white matter remote from lesions and in the gliotic lesion center. Ia antigen and human leukocyte antigen ABC on astrocytes were distributed similarly to IFN-gamma and IFN-beta, respectively. These findings indicate that IFN-gamma may play a role in active lesion growth in multiple sclerosis, whereas IFN-alpha and IFN-beta may exert some local immunosuppressive effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Traugott
U
U
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.
Lebon
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D001253:Astrocytes / Q000032:analysis* / Q000473:pathology; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007372:Interferons / Q000032:analysis*; D008264:Macrophages / Q000032:analysis* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology; D009422:Nervous System Diseases / Q000276:immunology / Q000473:pathology
D000911:Antibodies, Monoclonal; D007372:Interferons