Thalidomide suppresses up-regulation of human immunodeficiency virus coreceptors CXCR4 and CCR5 on CD4(+) T cells in humans

Concurrent infection in patients with human immunodeficiency virus (HIV) in fection increases the expression of HIV coreceptors CXCR4 and CCR5, Thalido mide has beneficial effects in a number of HIV-associated diseases. The eff ect of thalidomide on CXCR4 and CCR5 expression on CD4(+) T cells was deter mined. Thalidomide produced a dose-dependent inhibition of lipopolysacchari de (LPS)-induced up-regulation of CXCR4 and CCR5 in vitro. Antibody to tumo r necrosis factor-alpha (TNF-alpha) also attenuated the LPS-induced HIV cor eceptor up-regulation, which was not further reduced by thalidomide. Thalid omide (400 mg) was orally administered to 6 men, and their blood was stimul ated ex vivo with LPS, staphylococcal or mycobacterial antigens, or antibod y to CD3 or CD28 cells. All stimuli induced up-regulation of HIV coreceptor s, which was reduced after ingestion of thalidomide. Thalidomide may be ben eficial in the treatment of intercurrent infections during HIV infection by reducing the up-regulation of CXCR4 and CCR5 expression on CD4(+) T cells induced by bacterial and mycobacterial antigens, by a mechanism that involv es inhibition of TNF-alpha.