Time-course of interleukin-2 receptor expression in interferon beta-treated multiple sclerosis patients.
The time-course of CD25 (the 55-kD/alpha subunit of the interleukin-2 (IL-2) receptor) expression on CD4+ T lymphocytes, and serum levels of soluble IL-2 receptors (sIL-2R) and IL-2 were evaluated in relapsing-remitting multiple sclerosis (RRMS) patients treated with interferon beta-1b (IFNbeta1b). Peripheral blood samples were collected before therapy (T0), and 1 (T1), 2 (T2), 3 (T3), 6 (T4), and 12 (T5) months after therapy initiation. While at T1 and T2, half the patients showed an increased number of circulating CD4+ CD25+ lymphocytes and an up-regulation of CD25 expression, at T3 this T-cell subset was significantly reduced in all the patients. From T4 to T5, however, the progressive return to pretreatment values was observed. Serum sIL-2R levels were not significantly affected by IFNbeta1b at any time point. IL-2 was detected in only a few patients at T0, and never at T1 to T5. The transient up-regulation of CD25+ expression that occurred in about 50% of the patients may explain the unchanged relapse rate observed during the first 2 to 3 months after starting IFNbeta1b therapy. Our study demonstrates that IFNbeta1b down-regulates CD25 expression in vivo. This effect, however, was observed only after 3 months of therapy, and was followed by the return to pretreatment values after 6 to 12 months. Taken all together, our findings suggest that IFNbeta1b only transiently affects CD25 expression in vivo, and that this effect cannot account for the reported long-lasting beneficial action of IFNbeta1b on RRMS.
Ferrarini
A M
AM
Department of Neurological and Psychiatrical Sciences, Second Neurological Clinic, University of Padova, Italy.
Sivieri
S
S
Bulian
P
P
Buttarello
M
M
Biasi
G
G
Tavolato
B
B
Gallo
P
P
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016899:Interferon-beta / Q000008:administration & dosage* / Q000276:immunology; D008137:Longitudinal Studies; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D010352:Patient Dropouts; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000096:biosynthesis* / Q000097:blood; D013997:Time Factors
D000276:Adjuvants, Immunologic; D001323:Autoantibodies; D015375:Receptors, Interleukin-2; D016899:Interferon-beta