Inhibition of de novo IgM antibody synthesis by thalidomide as a relevant mechanism of action in leprosy.

Thalidomide is well documented to be an effective treatment for erythema nodosum leprosum (ENL) occurring in lepromatous leprosy. To be beneficial, thalidomide must interfere with one or more of the several essential steps in the pathogenesis of this syndrome, which is presumed to be a clinical manifestation of an Arthur-type hypersensitivity. Since complexes of antigen and antibody would initiate these events, thalidomide could exert its most direct influence on reactants in this essential step. To determine whether thalidomide affected de novo antibody synthesis, the effect of the drug on the antibody response to sheep erythrocytes in mice was determined. Thalidomide significantly inhibited IgM antibody formation when fed to mice for 5 or 7 days before immunization with sheep erythrocytes. There was also a selective decrease in serum IgM concentrations among leprosy patients being treated with thalidomide for ENL. A clinically relevant site of action of thalidomide in ENL appears to be on the synthesis of IgM antibody. The target site of the drug among the macrophage, antibody-forming, and helper or suppressor lymphocytes remains to be elucidated.