Comparative effects of interferon-consensus 1, interferon-alpha 2a, and interferon-beta 1b on HLA expression and lymphoproliferation: a preclinical model for treatment of multiple sclerosis.
Interferon-consensus 1 (IFN-Con 1) is a novel synthetic protein generated from codons for the most frequent amino acids in different type 1 IFNs. Compared with natural IFNs, IFN-Con 1 has been shown to have higher specific activity and antiproliferative activity and a higher ability to induce natural killer cells. In this study, the effects of IFN-Con 1 were compared with those of IFN-beta 1b and IFN-alpha 2a on HLA expression and lymphoproliferation. Human umbilical vein endothelial cells (HUVEC) express HLA class I but not class II molecules; however, both class I and class II molecules can be upregulated by IFN-gamma. IFN-Con-1 shared with IFN-beta 1b and IFN-alpha 2a the capacity to enhance HLA class I expression on HUVEC, alone and in combination with IFN-gamma. Although IFN-Con 1 had no effect on the basal expression of HLA class II molecules, it inhibited the IFN-gamma-induced class II expression on the HUVEC in a dose-dependent fashion. When this effect was compared among the three IFNs on mass basis, IFN-Con 1 activity was intermediate between that of IFN-beta 1b and IFN-alpha 2a. IFN-Con 1 also demonstrated an inhibitory effect on mitogen-driven lymphoproliferation similar to that of IFN-alpha 2a and exceeded that of IFN-beta 1b. The results indicate that IFN-Con 1 has immunomodulatory effects similar to those of IFN-beta 1b and IFN-alpha 2a, which could be relevant to the treatment of autoimmune and virus-mediated diseases.
Dhib-Jalbut
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Department of Neurology, University of Maryland at Baltimore 21201, USA.
Jiang
H
H
Xia
Q
Q
Blatt
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L
Johnson
K P
KP
Hilt
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D
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D002460:Cell Line; D003208:Concanavalin A / Q000037:antagonists & inhibitors; D004353:Drug Evaluation, Preclinical; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D000077190:Interferon alpha-2; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D008232:Lymphoproliferative Disorders / Q000188:drug therapy / Q000276:immunology; D009103:Multiple Sclerosis / Q000188:drug therapy*; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000949:Histocompatibility Antigens Class II; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D003208:Concanavalin A; D000068576:Interferon beta-1b; C050739:interferon alfacon-1; D016899:Interferon-beta; D000068556:Interferon beta-1a