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

Danish Multiple Sclerosis Research Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Copenhagen, Denmark, martin.krakauer{at}dadlnet.dk

P Sorensen

Danish Multiple Sclerosis Research Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Copenhagen, Denmark

M Khademi

Department of Clinical Neurosciences, Karolinska University Hospital, Neuroimmunology Unit CMM, Stockholm, Sweden

T Olsson

Department of Clinical Neurosciences, Karolinska University Hospital, Neuroimmunology Unit CMM, Stockholm, Sweden

F Sellebjerg

Danish Multiple Sclerosis Research Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Copenhagen, Denmark

Background

Interferon (IFN)-β 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-β therapy in MS.

Methods

Twenty patients with relapsing–remitting MS were sampled before and after 3 months of treatment with IFN-β 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-β 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 (~9–12 h) after an IFN-β injection.

Conclusion

We found no evidence of a Th1- or Th2-mRNA-promoting effect of IFN-β therapy. The therapeutic effect of IFN-β 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-β therapy resulted in decreased IL-23 mRNA levels, the Th17 axis could be another target of IFN-β therapy.

Key Words: autoimmune diseases • cytokines • immunotherapy • interferon-β treatment • interleukin-10 • interleukin-23 • multiple sclerosis

This version was published on June 1, 2008

Multiple Sclerosis, Vol. 14, No. 5, 622-630 (2008)
DOI: 10.1177/1352458507087136


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