Monocytes from patients with myelodysplastic syndromes are more resistant to inhibition by thalidomide

The myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal hematopoietic disorders characterized by cytopenias and marrow dysplasia. Immune mechanisms are in part responsible for the marrow failure observed in MDS patients [1]. We have recently provided evidence for the involvement of CD40-CD40L interactions between monocytes with T helper cells in the pathogenesis of this marrow failure [2]. More specifically, we have shown that monocytes from MDS patients produce more TNF-α in response to stimulation of the CD40-receptor than control monocytes. Thalidomide is a potent immune-modulating agent with a broad spectrum of immunologic effects and has been used in MDS patients as single-agent therapy [3-5] or in combination with other agents [6-9]. Inhibition of TNF-α production is believed to be the primordial mechanism by which thalidomide acts in MDS. However, in vitro data on the effect of thalidomide on TNF-α production in MDS currently lack. With this study, we provide the first data of the effect of increasing doses of thalidomide on the production of TNF-α by monocytes from MDS patients in response to lipopolysaccharide (LPS) or CD40-agonists. We show that only a high concentration of thalidomide is able to inhibit the TNF-α production of MDS monocytes stimulated by CD40-agonists.status: publishe