Lobenzarit disodium (CCA) inhibits in vitro immunoglobulin production via direct interaction with B lymphocytes

The regulatory effects of lobenzarit disodium (CCA), a therapeutic agent for treating rheumatoid arthritis (RA), on polyclonal immunoglobulin production by human lymphocytes were investigated in vitro. CCA inhibited the production of immunoglobulin in all the classes examined at a clinically relevant concentration. Moreover, it inhibited the immunoglobulin production as well as lymphocyte proliferation even when purified B lymphocytes preactivated by Staphylococcus aureus COWAN I were cultured with recombinant lymphokines such as IL2 and IL6. These results suggest that CCA acts directly on B lymphocytes. The analysis at each of two different stages of B lymphocyte activation lineage, i.e., the primary activation stage and a stage of proliferation and differentiation to antibody secreting cells, has indicated that CCA inhibits the proliferation-differentiation stage of B lymphocytes. CCA does not inhibit B lymphocytes at the primary activation stage; actually, it augments them, resulting in the subsequent enhancement of immunoglobulin production.