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Randomized Controlled Trial
. 2007 Apr;185(1-2):168-74.
doi: 10.1016/j.jneuroim.2007.01.011. Epub 2007 Feb 27.

Cytokine changes during interferon-beta therapy in multiple sclerosis: correlations with interferon dose and MRI response

Affiliations
Randomized Controlled Trial

Cytokine changes during interferon-beta therapy in multiple sclerosis: correlations with interferon dose and MRI response

Jerome J Graber et al. J Neuroimmunol. 2007 Apr.

Abstract

We investigated serum (IL-10 and IL-12p70) and cellular cytokine levels (IL-10, IL-12p40, IL-12p70, IFN-gamma) in stimulated PBMC over 24 weeks in 15 relapsing-remitting multiple sclerosis (MS) patients randomized to receive once-weekly (qw) IFN-beta-1a 30 microg intramuscularly (IM) (n=8) or three-times-weekly (tiw) IFN-beta-1a 44 microg subcutaneously (SC) (n=7). Overall, IFN-beta treatment increased cellular IL-10 (p<0.01) levels and the ratios of cellular IL-10/IL-12p40 (p<0.01) and IL-10/IL-12p70 (p<0.02) while cellular IFN-gamma levels were reduced (p<0.01). Serum IL-10 levels were decreased in non-responders to therapy based on MRI-defined criteria (p<0.01) but did not change in responders over the course of treatment. In addition, non-responders demonstrated a decrease in serum IL-10/IL-12p70 ratio (p=0.031) and a decrease in cellular IL-12p70 (p<0.02). A decrease in cellular IFN-gamma was observed in responders (p=0.013). This is the first study that compares cytokine changes between the two IFN-beta regimes and demonstrates that serum IL-10 levels decrease in those patients who continue to have active MRI lesions while on interferon-beta therapy.

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Figures

Figure 1
Figure 1
Serum levels of interleukin-10 were lower in non-responders (as defined by cumulative unique MRI lesions) over the course of 24 weeks of IFN-β therapy compared to non-responders. Standard error bars are shown.
Figure 2
Figure 2
Levels of ex vivo cellular production of interleukin-12p70 over the course of 24 weeks of IFN-β therapy were lower in the group of non-responders compared to responders. Overlapping error bars are removed for clarity.
Figure 3
Figure 3
Levels of ex vivo cellular production of interferon-gamma decreased compared to baseline over the course of IFN-β therapy in the total group on any IFN-β therapy (p<0.001) and in the group of responders (p=0.013). Compared to non-responders, IFN-gamma levels were lower on treatment in responders (p=0.005). Overlapping error bars are removed for clarity.

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