Cytokine changes during interferon-beta therapy in multiple sclerosis: correlations with interferon dose and MRI response.
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.
Graber
Jerome J
JJ
University of Maryland School of Medicine, Department of Neurology, MD, USA.
Ford
David
D
Zhan
Min
M
Francis
Gordon
G
Panitch
Hillel
H
Dhib-Jalbut
Suhayl
S
D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D016899:Interferon-beta / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000032:analysis / Q000187:drug effects; D016753:Interleukin-10 / Q000032:analysis / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000032:analysis / Q000096:biosynthesis; D053762:Interleukin-12 Subunit p40 / Q000032:analysis / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology
D007155:Immunologic Factors; D053762:Interleukin-12 Subunit p40; D016753:Interleukin-10; D018664:Interleukin-12; D016899:Interferon-beta; D007371:Interferon-gamma