Interferon-beta interferes with the proliferation but not with the cytokine secretion of myelin basic protein-specific, T-helper type 1 lymphocytes.
Interferon-beta (IFN-beta) has beneficial effects on the frequency and severity of relapses, as well as on disease progression in patients suffering from relapsing-remitting MS. Its mode of action, however, is not completely understood. Previous studies on T-lymphocyte bulk cultures and T-lymphocyte lines with specificity for different antigens suggested that the drug might partially act via suppression of T-cell proliferation and secretion of proinflammatory cytokines like interferon-gamma (IFN-gamma) and/or tumor necrosis factor-alpha (TNF-alpha). In this study we investigated the effects of human recombinant IFN-beta 1b on proliferation, interleukin 2 (IL-2) receptor (IL-2R) alpha-chain upregulation, and cytokine and chemokine secretion of myelin basic protein-reactive, MS patient-derived T-cell clones secreting T-helper type 1 (Th1) cytokines. IFN-beta partially suppressed both antigen- and IL-2-driven proliferation of these cells without affecting the expression of either IL-2 or IL-2R alpha-chain. There was no inhibitory effect on the secretion of IFN-gamma, TNF-alpha, and macrophage inflammatory protein (MIP)-1 alpha, but release was rather slightly enhanced. In conclusion, while IFN-beta does reduce proliferation of Th1-like, MBP-specific T cells in vitro, the drug does not result in overall dysfunction of these cells. Therefore, the effect of IFN-beta on MS may not depend on a primary inhibition of potentially encephalitogenic T lymphocytes.
Pette
M
M
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1400, USA.
Pette
D F
DF
Muraro
P A
PA
Farnon
E
E
Martin
R
R
McFarland
H F
HF
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D004676:Myelin Basic Protein / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D000276:Adjuvants, Immunologic; D016207:Cytokines; D007376:Interleukin-2; D004676:Myelin Basic Protein; D015375:Receptors, Interleukin-2; D016899:Interferon-beta