Interferon-beta therapy for multiple sclerosis induces reciprocal changes in interleukin-12 and interleukin-10 production.
Ann Neurol
; 51(2): 165-74, 2002 Feb.
Article
em En
| MEDLINE
| ID: mdl-11835372
Interleukin-12 is critical to the pathogenesis of experimental autoimmune encephalomyelitis in multiple species. Interleukin-10, a dominant endogenous inhibitor of interleukin-12, is largely protective in these experimental surrogates for multiple sclerosis. Such data have suggested that an interleukin-12/interleukin-10 immunoregulatory circuit is a key determinant of disease expression in experimental autoimmune encephalomyelitis. For multiple sclerosis itself, compatible cytokine data have been reported. The mechanisms underlying the beneficial effects of interferon-beta in multiple sclerosis remain unclear, hampering the search for more effective therapies. Of note, interferon-beta has reciprocal effects on these cytokines in vitro, suppressing interleukin-12 and augmenting interleukin-10 production. To examine the effects of interferon-beta on the interleukin-12/interleukin-10 axis in multiple sclerosis, we characterized the production of these cytokines by peripheral blood mononuclear cells from patients beginning therapy with interferon-beta. Before therapy, multiple sclerosis patients exhibited increased stimulatable interleukin-12 production compared with controls. Interferon-beta therapy leads to inhibition of interleukin-12 and augmentation of interleukin-10 production, significantly elevating the ratio of secreted interleukin-10 to interleukin-12. These effects, observed equally in patients with relapsing-remitting and progressive disease, indicate that interferon-beta affects the interleukin-12/interleukin-10 axis in ways thought to be beneficial to multiple sclerosis patients. More specific therapeutic targeting of these pathways may be warranted.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Adjuvantes Imunológicos
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Interleucina-10
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Interferon beta
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Interleucina-12
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Esclerose Múltipla Recidivante-Remitente
Limite:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Ann Neurol
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Estados Unidos