THE EFFECTS OF THALIDOMIDE TREATMENT ON AUTOIMMUNE-PRONE NZB AND MRL MICE ARE CONSISTENT WITH STIMULATION OF THE CENTRAL IMMUNE-SYSTEM .2.

We describe here some immunomodulatory effects of thalidomide on autoi mmune-prone mice. The highly increased synthesis of splenic IgM in NZB mice, of splenic and lymph node IgG of different subclasses in MRL/n mice, and of splenic and lymph node IgG1 in MRL/lpr mice was markedly inhibited by thalidomide treatment. After a single treatment with 3 mg of thalidomide, the following changes were observed in NZB mice: (i) an initial decrease in the numbers of large CD5(+)mu(high), and in the numbers of total CD5(+)mu(-), CD5(-)mu(high) CD5(+)mu(high) lymphocyt e populations of the pleural cavity followed by a late increase in the numbers of large cells of the three cell populations; (ii) a consiste nt increase in the numbers of a CD5(low) mu(low) pleural lymphoid popu lation; (iii) a consistent reduction in the numbers of splenic large C D5(+) B cells and an oscillatory increase in the number of cells with CD5(-) phenotype; (iv) a late reduction in the numbers of splenic tota l CD5(+) B cells. These results are consistent with the notion that th alidomide controls a disease-associated expansion of B cells in autoim mune prone mouse strains through a stimulatory effect of the drug on t he immune system.