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.