The effects of thalidomide treatment on autoimmune-prone NZB and MRL mice are consistent with stimulation of the central immune system.

Abstract

We describe here some immunomodulatory effects of thalidomide on autoimmune-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+ microhigh, and in the numbers of total CD5+ micro-, CD5- microhigh, CD5+ microhigh lymphocyte populations of the pleural cavity followed by a late increase in the numbers of large cells of the three cell populations; (ii) a consistent increase in the numbers of a CD5low microlow pleural lymphoid population; (iii) a consistent reduction in the numbers of splenic large CD5+ B cells and an oscillatory increase in the number of cells with CD5- phenotype; (iv) a late reduction in the numbers of splenic total CD5+ B cells. These results are consistent with the notion that thalidomide controls a disease-associated expansion of B cells in autoimmune prone mouse strains through a stimulatory effect of the drug on the immune system.