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Increased IL-10 mRNA and IL-23 mRNA expression in multiple sclerosis: interferon-beta treatment increases IL-10 mRNA expression while reducing IL-23 mRNA expression

Increased IL-10 mRNA and IL-23 mRNA expression in multiple sclerosis: interferon-beta treatment increases IL-10 mRNA expression while reducing IL-23 mRNA expression

Multiple Sclerosis 14(5): 622-630

Background Interferon ( IFN)-beta therapy in multiple sclerosis ( MS) has been suggested to promote a deviation from T lymphocyte production of pathogenic Th1 cytokines to less detrimental Th2 cytokines, but this is still controversial. We studied patterns of in vivo blood mononuclear cell ( MNC) and whole blood cytokine and transcription factor mRNA expression before and during IFN-beta therapy in MS.Methods Twenty patients with relapsing-remitting MS were sampled before and after 3 months of treatment with IFN-beta along with 15 healthy volunteers. An additional 39 patients and 50 healthy volunteers served to confirm initial findings. mRNA was analyzed by real-time reverse transcriptase polymerase chain reaction (PCR).Results We found elevated expression of interleukin ( IL)-23 and IL-10 in untreated MS patients. IFN-beta therapy increased IL-10 and decreased IL-23 expression independently of any Th1 or Th2 cytokines. The largest changes in cytokine mRNA levels occurred early (similar to 9-12 h) after an IFN-beta injection.Conclusion We found no evidence of a Th1- or Th2- mRNA- promoting effect of IFN-beta therapy. The therapeutic effect of IFN-beta is more likely attributable to the induction of the regulatory cytokine IL-10. The elevated IL-23 mRNA levels in MS patients are noteworthy in view of the newly discovered IL-23- driven Th17 T-cell subset, which is crucial in animal models of MS. Since IFN-beta therapy resulted in decreased IL-23 mRNA levels, the Th17 axis could be another target of IFN-beta therapy.

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Accession: 031883326

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PMID: 18424480

DOI: 10.1177/1352458507087136

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