IFNbeta-1a treatment and reestablishment of Th1 regulation in MS patients: dose effects.
The authors evaluated the relationships between clinical and pharmacologic parameters and the Th1/Th2/Th3 cytokine network in patients with relapsing-remitting multiple sclerosis treated with differing doses of interferon-beta1a (IFN-beta1a). Their results show that low doses are ineffective but that high doses restore Th1 regulation of the maturation and activation of monocytes, T cells, immature dendritic cells, dendritic cells, and T regulatory cells for central and peripheral self-tolerance. Interaction between interleukin (IL)-10, IL-12 p70, and IL-6 production appears to play an important role in the control of the maturation and activation states of dendritic cells and T regulatory cells, and is at the basis of the benefit of high doses. The results also indicate that the physiologic mechanisms involved in aging help immunologic reestablishment in IFNbeta-1a-treated patients. Finally, it would appear that the failure of IFNbeta-1a therapy to resolve multiple sclerosis completely is due to the suppression of IL-12 p70 mechanisms (responsible for the physiologic deletion of self-reactive cells) in activation conditions, probably by IFNbeta-1a itself.
Pellegrini
Patrizia
P
Istituto CNR per i Trapianti d'Organo e l'Immunocitologia, L'Aquila, Italia. ittppp12@area.ba.cnr.it
Totaro
Rocco
R
Contasta
Ida
I
Berghella
Anna Maria
AM
Russo
Tomassina
T
Carolei
Antonio
A
Adorno
Domenico
D
D000328:Adult; D001773:Blood Cells / Q000166:cytology / Q000187:drug effects; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis / Q000097:blood; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D016899:Interferon-beta / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009000:Monocytes / Q000166:cytology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D018709:Statistics, Nonparametric; D018417:Th1 Cells / Q000187:drug effects*; D018418:Th2 Cells / Q000187:drug effects
D016207:Cytokines; D007155:Immunologic Factors; D016899:Interferon-beta