The effect of beta-interferon therapy on myelin basic protein-elicited CD4+ T cell proliferation and cytokine production in multiple sclerosis.
Interferon (IFN)-beta therapy has well-established clinical benefits in multiple sclerosis (MS), but the underlying modulation of cytokine responses to myelin self-antigens remains poorly understood. We analysed the CD4+ T cell proliferation and cytokine responses elicited by myelin basic protein (MBP) and a foreign recall antigen, tetanus toxoid (TT), in mononuclear cell cultures from fourteen MS patients undergoing IFN-beta therapy. The MBP-elicited IFN-gamma-, TNF-alpha- and IL-10 production decreased during therapy (p<0.007-0.03), while the IL-6 production increased (p<0.03). No significant change was observed in the MBP-induced CD4+ T cell proliferation, or in the production of IL-4, IL-5 and brain-derived neurotrophic factor. In comparison, IFN-beta therapy reduced IFN-gamma and IL-4 responses to TT (p<0.003 and p<0.04). Thus, IFN-beta inhibits IFN-gamma production in general, presumably alleviating the detrimental influence of IFN-gamma in MS. However, the increase in proinflammatory IL-6 and the decrease in anti-inflammatory IL-10 responses suggest that IFN-beta has more diverse effects than previously assumed.
Hedegaard
Chris J
CJ
Institute for Inflammation Research, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
Krakauer
Martin
M
Bendtzen
Klaus
K
Sørensen
Per Soelberg
PS
Sellebjerg
Finn
F
Nielsen
Claus H
CH
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D004676:Myelin Basic Protein / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology
D016207:Cytokines; D004676:Myelin Basic Protein; D013745:Tetanus Toxoid; D016899:Interferon-beta