[T-cell interferon-gamma, tumor necrosis factor-alpha and interleukin-6 receptor binding in patients with multiple sclerosis. Effects of interferon-beta-1b treatment].
BACKGROUND
Multiple sclerosis (MS) is a T-cell-mediated demyelinating disease of the central nervous system (CNS), in which the cytokine network may be deranged. Interferon (IFN)-gamma, interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha are cytokines with several effects on the neuroimmune system. Specific IFN-gamma, IL-6, and TNF-alpha receptors have been found on human lymphocytes and other cell types.


METHODS
We assayed IFN-gamma, TNF-alpha, and IL-6 binding on peripheral blood T cells from MS patients, as compared with healthy subjects. T cells from MS patients have significantly less IFN-gamma receptors, and more TNF-alpha and IL-6 receptors than those from controls. Such receptors are of the same type in patients and healthy subjects. By comparing MS patients' subgroups with each other, significant differences in mean Bmax values have been found between patients in a stable phase and those in relapse, and between stable patients and those in an evolutive phase. As far as IL-6 binding is concerned, significant differences in mean Bmax values were observed only between patients in stable phase and those in relapse.


RESULTS
T lymphocytes from untreated MS patients, which had significantly smaller amounts of IFN-gamma receptors than those from controls, and more TNF-alpha and IL-6 receptors than controls showed a significant increase in IFN-gamma binding, and a significant decrease in TNF-alpha and IL-6 binding after a 3-month IFN-beta 1b treatment. T-cell IFN-gamma Bmax values were even higher, and those of TNF-alpha and IL-6 were lower after 6 months.


CONCLUSIONS
We discuss these results in terms of MS immunopathophysiology, since activated T cells have decreased IFN-gamma, and increased TNF-alpha and IL-6 receptor amounts.
Bongioanni
P
P
Departamento de Neurociencias, Universidad de Pisa, Italia. bongioanni@sssup.it
Romano
M R
MR
Boccardi
B
B
Lombardo
F
F
Moscato
G
G
Mosti
S
S
Baldini
C
C
Nuti
S
S
Meucci
G
G
Rossi
B
B
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D001667:Binding, Competitive; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000378:metabolism*; D017471:Receptors, Interferon / Q000187:drug effects / Q000378:metabolism*; D019947:Receptors, Interleukin-6 / Q000187:drug effects / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects / Q000378:metabolism*; D012008:Recurrence
D000276:Adjuvants, Immunologic; D011948:Receptors, Antigen, T-Cell; D017471:Receptors, Interferon; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D000068576:Interferon beta-1b; D016899:Interferon-beta; D007371:Interferon-gamma; D000068556:Interferon beta-1a