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.
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 (~9-12 h) after an IFN-beta injection.


CONCLUSIONS
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.
Krakauer
M
M
Danish Multiple Sclerosis Research Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Copenhagen, Denmark. martin.krakauer@dadlnet.dk
Sorensen
P
P
Khademi
M
M
Olsson
T
T
Sellebjerg
F
F
D015415:Biomarkers / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D053759:Interleukin-23 / Q000235:genetics* / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000187:drug effects / Q000502:physiology; D018418:Th2 Cells / Q000187:drug effects / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics
D015415:Biomarkers; C508609:IL10 protein, human; D007155:Immunologic Factors; D053759:Interleukin-23; D012333:RNA, Messenger; D014157:Transcription Factors; D016753:Interleukin-10; D016899:Interferon-beta