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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Abstract
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 patients 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 patients 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 patients under investigation. Ann Neurol 2000;48:313–322

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