GLATIRAMER ACETATE BLOCKS THE ACTIVATION OF THP-1 CELLS BY INTERFERON-GAMMA

Glatiramer acetate (previously known as copolymer I) is a synthetic co polymer of four amino acids that has been approved for use in the trea tment of multiple sclerosis. It has been shown to suppress myelin anti gen specific T cell activation by competing with these antigens at the major histocompatibility complex class II binding site and by inducin g antigen specific suppressor T cells. In this study we investigated t he effects of glatiramer acetate on the human monocytic cell line, THP -1, activated by lipopolysaccharide and interferon-gamma as a model fo r macrophages. At non-toxic concentrations of glatiramer acetate there were dose dependent reductions in the percentage of cells expressing human leukocyte DR and DQ antigen as well as in mean fluorescence inte nsity by flow cytometry. Production of tumor necrosis factor-alpha and the lysosomal cysteine proteinase cathepsin B were markedly-inhibited , but production of interleukin-l increased. These results suggest tha t glatiramer acetate might alter macrophage effector function and sugg est that further studies in human monocytes and macrophages are warran ted. Published by Elsevier Science B.V.