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

Abstract

We investigated serum (IL-10 and IL-12p70) and cellular cytokine levels (IL-10, IL-12p40, IL-12p70, IFN-γ) in stimulated PBMC over 24 weeks in 15 relapsing–remitting multiple sclerosis (MS) patients randomized to receive once-weekly (qw) IFN-β-1a 30 μg intramuscularly (IM) ( n = 8) or three-times-weekly (tiw) IFN-β-1a 44 μg subcutaneously (SC) ( n = 7). Overall, IFN-β 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-γ 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-γ was observed in responders ( p = 0.013). This is the first study that compares cytokine changes between the two IFN-β regimes and demonstrates that serum IL-10 levels decrease in those patients who continue to have active MRI lesions while on interferon-beta therapy.