Effect of thalidomide on induction of antibody synthesis in mice to the T-independent antigen, DNP-Ficoll

Abstract

Summary Thalidomide enhances de novo IgM antibody synthesis in mice to DNP Ficoll. The immunocompetent cells responsive to thymic independent antigens like DNP-Ficoll are macrophages and the B lymphocytes. Enhancement ofimmunores ponsiveness to DNP-Ficoll seems to be due to augmentation of macrophage fu nction by thalidomide.Since 1965, thalidomide has been used in alleviating the signs and symptoms of a major medical complication of lepromatous leprosy, erythema nodosum lepro sum (ENL).I Histologically, the hallmarks of ENL lesions are vasculitis or vascular necrosis, oedema and inflammation with infiltrates of neutrophils affecting the entire dermis and subcutaneous fa t.2 The factor or fa ctors that trigger the influx of neutrophils is unknown. For thalidomide to be effective in ENL, it must interfere with one or more of the essential steps in the pathogenesis of this syndrome.Since it has been suggested that ENL is an immune complex mediated disease,3, 4 we have investigated the effect of thalidomide on humoral immunolo gical responses. Thalidomide significantly inhibits an IgM but · not an IgG response in mice to the T-cell-dependent antigen, sheep erythrocytes; it also selectively decreases serum IgM concentrations among leprosy patients being treated fo r their ENL. 5 These observations have prompted us to speculate that a clinically relevant site of action fo r thalidomide in ENL is on the synthesis ofIgM antibody. If thalidomide acts on immunocompetent cells, the cell target of the drug must be among the macrophage, IgM antibody fo rming B cell and helper or suppressor lymphocytes.0305-75 18/85/056297 + 05 SO 1 .00

I. Immunostimulatory Effect of Thalidomide in Normal C57BL/6 Mice is Compatible with Stimulation of a Highly Connected Central Immune System

“…injection with thalidomide. On the contrary, the previous observations of enhancement of B-cell numbers [40] and responses [41 ], and the presently reported increases in the numbers of non-specific and specific natural anti-SRBC splenic secreting PFC, and of total and large CD5^ or CDS B cells, after treatment with thalidomide, suggest that the latter stimulates the immune system. Several of the present results also indicate that both CIS and PIS are stimulated by thalidomide.…”