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

Abstract

Although thalidomide has been used with success in the treatment of increasing numbers of autoimmune diseases, the therapeutic effects have not been satisfactorily explained so far. We describe here some findings that may contribute to a better understanding of the immunomodulatory effects of this drug. Several immunological changes were observed after treating C57BL/6 mice with 3 mg of thalidomide. The numbers of natural IgM PFC against sheep red blood cells were increased in the spleen, and occasionally a dramatic oscillatory increase in the numbers of non-specific splenic IgM and IgG PFC was observed in these mice. However, these oscillatory increases were progressively lower, after two and three treatments with thalidomide at 20-day intervals. Furthermore, the absolute numbers of splenic CD5+ B and CD5- B lymphocytes were increased whereas depletion of CD4+ CD8+ cells in the thymus and of lymphoid cells in the bone marrow was seen after a single treatment with 3 mg of thalidomide. Taken together, these results suggest that thalidomide stimulates both peripheral and central immune systems and consequently enhances the connectivity of the central immune system.

Downregulation of myeloma-induced ICOS-L and regulatory T cell generation by lenalidomide and dexamethasone therapy

“…Whilst demonstrating discrete anti-myeloma effects, many of these agents have also shown potential anti-tumour immune effects [13][14][15][16]. The IMiDs (thalidomide, lenalidomide and pomalidomide) in particular have not only shown great promise in the clinic as tumouricidal agents but also have immune skewing functions which may contribute to their anti-myeloma effect.…”

Thalidomide inhibited the synthesis of IgM and IgG whereas Thalidomide+Dexamethasone and Dexamethasone alone acted as co-stimulants with pokeweed and enhanced their synthesis

“…Some investigators show suppression of antibody synthesis by Thal [24], while others show enhancement [25,26].…”