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) infection increases the expression of HIV coreceptors CXCR4 and CCR5. Thalidomide has beneficial effects in a number of HIV-associated diseases. The effect of thalidomide on CXCR4 and CCR5 expression on CD4+ T cells was determined. Thalidomide produced a dose-dependent inhibition of lipopolysaccharide (LPS)-induced up-regulation of CXCR4 and CCR5 in vitro. Antibody to tumor necrosis factor-alpha (TNF-alpha) also attenuated the LPS-induced HIV coreceptor up-regulation, which was not further reduced by thalidomide. Thalidomide (400 mg) was orally administered to 6 men, and their blood was stimulated ex vivo with LPS, staphylococcal or mycobacterial antigens, or antibody to CD3 or CD28 cells. All stimuli induced up-regulation of HIV coreceptors, which was reduced after ingestion of thalidomide. Thalidomide may be beneficial 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 involves inhibition of TNF-alpha.
Juffermans
N P
NP
Laboratory of Experimental Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. N.Juffermans@amc. uva.nl.
Verbon
A
A
Olszyna
D P
DP
van Deventer
S J
SJ
Speelman
P
P
van Der Poll
T
T
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D006678:HIV / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D019713:Receptors, CCR5 / Q000032:analysis / Q000235:genetics*; D019718:Receptors, CXCR4 / Q000032:analysis / Q000235:genetics*; D012016:Reference Values; D013792:Thalidomide / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
D008070:Lipopolysaccharides; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D013792:Thalidomide