Comparative Effects of Interferon-Consensus 1,Interferon-α 2a,and Interferon-/β lb on HLA Expression and Lymphoproliferation: A Preclinical Model for Treatment of Multiple Sclerosis

Abstract

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-β_1b and IFN-α_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-γ. IFN-Con-1 shared with IFN-β_1b and IFN-α_2a the capacity to enhance HLA class I expression on HUVEC, alone and in combination with IFN-γ. Although IFN-Con 1 had no effect on the basal expression of HLA class II molecules, it inhibited the IFN-γ-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-β_1b and IFN-α_2a. IFN-Con 1 also demonstrated an inhibitory effect on mitogen-driven lymphoproliferation similar to that of IFN-α_2a and exceeded that of IFN-β_1b. The results indicate that IFN-Con 1 has immunomodulatory effects similar to those of IFN-β_1b and IFN-α_2a, which could be relevant to the treatment of autoimmune and virus-mediated diseases.