Interferon beta induces interleukin-10 expression: relevance to multiple sclerosis.
Interferon-beta decreases the relapse rate, relapse severity, progression of neurological disability, and development of new brain lesions observed with brain magnetic resonance imaging in relapsing-remitting multiple sclerosis patients. The mechanism of action of this effect is presently unknown. This study was based on the hypothesis that immunoregulatory effects of interferon-beta may underlie its demonstrated clinical efficacy. The objective of the study was to determine the effect of interferon-beta-1a on the expression of interleukin-10, a cytokine that strongly inhibits cell-mediated immune responses. Interferon-beta-1a induced accumulation of interleukin-10 messenger RNA and protein secretion by cultured peripheral blood mononuclear cells. The observed in vitro effects were similar for healthy control subjects and multiple sclerosis patients. Intramuscular injections of interferon-beta-1a increased serum levels of interleukin-10 at 12 and 24 hours following the injection. Greater increases were induced with 12 x 10(6)-IU than 6 x 10(6)-IU injections. The effect of interferon-beta-1a was relatively specific for interleukin-10, as treatment with interferon-beta-1a did not result in accumulation of transforming growth factor-beta messenger RNA. Upregulation of interleukin-10 represents a possible mechanism of action of interferon-beta's therapeutic effect in relapsing-remitting multiple sclerosis, and has implications for therapy of other autoimmune diseases.
Rudick
R A
RA
Department of Neurology (Mellen Center), Cleveland Clinic Foundation, OH 44106, USA.
Ransohoff
R M
RM
Peppler
R
R
VanderBrug Medendorp
S
S
Lehmann
P
P
Alam
J
J
D000911:Antibodies, Monoclonal; D001483:Base Sequence; D001921:Brain / Q000503:physiopathology; D018929:Cell Culture Techniques; D017931:DNA Primers; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007273:Injections, Intramuscular; D016899:Interferon-beta / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism*; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000503:physiopathology; D012333:RNA, Messenger
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D012333:RNA, Messenger; D016753:Interleukin-10; D016899:Interferon-beta