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Contrasting responses to interferon β-1b treatment in relapsing-remitting multiple sclerosis: Does baseline interleukin- 12p35 messenger RNA predict the efficacy of treatment?

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Author: Boxel van-Dezaire, A.H.H. · Trigt van-Hoff, S.C.J. · Killestein, J. · Schrijver, H.M. · Houwelingen, J.C. van · Polman, C.H. · Nagelkerken, L.
Institution: TNO Preventie en Gezondheid
Source:Annals of Neurology, 3, 48, 313-322
Identifier: 235665
doi: doi:10.1002/1531-8249(200009)48:3<313::AID-ANA5>3.0.CO;2-9
Keywords: Health · Gamma interferon · Interferon beta serine · Interleukin 10 · Interleukin 12 · Interleukin 12 receptor · Interleukin 18 · Messenger RNA · Protein p35 · Protein p40 · Clinical article · Disability · Disease classification · DNA synthesis · Drug efficacy · Gene expression · Multiple sclerosis · Prediction · Rating scale · Recurrent disease · Treatment outcome · Adult · Female · Humans · Interferon-beta · Interleukin-12 · Male · Multiple Sclerosis, Relapsing-Remitting · Predictive Value of Tests · RNA, Messenger · Time Factors


Interferon (IFN)-β treatment is effective in relapsing-remitting multiple sclerosis (RR-MS) via an as yet unidentified mechanism. In the present study, we investigated whether the expression of messenger RNA (mRNA) encoding the interleukin (IL)-12 subunits p40 and p35, IL-12 receptor chains, IL-18, tumor necrosis factor-α (TNFα), IFNγ, IL-10, IL-4, or transforming growth factor-β in unstimulated whole blood of 26 RR-MS patents changed during 6 months of IFNβ-1b treatment. In these patients, a significant change was found in TNFα mRNA, whereas changes in IL-12 receptor-β2 and IL-10 mRNA showed a trend. IFNβ-1b-related changes in cytokine mRNA expression were next evaluated in clinical subgroups of RR-MS patents classified as either clinical responders or nonresponders on the basis of Expanded Disability Status Scale progression and the number of relapses and steroid interventions needed in the 2 years before initiation of treatment compared with the 2 years after initiation of treatment. These subgroups showed different response patterns to IFNβ-1b treatment with respect to IL-10, TNFα, and IL-18 only. Surprisingly, clinical responders displayed no change in these cytokines, whereas nonresponders showed a decrease in TNFα and IL-18 mRNA as well as a transient increase in IL-10 mRNA. Baseline levels of IL-12p35 mRNA were lower in the responders compared with the nonresponders: this marker correctly predicted the clinical outcome in 81% of the 26 patents under investigation. Chemicals/CAS: interferon beta 1a, 145258-61-3; interferon beta-1b, 145155-23-3; Interferon-beta, 77238-31-4; Interleukin-12, 187348-17-0; RNA, Messenger