Cocaine amplifies HIV-1 replication in cytomegalovirus-stimulated peripheral blood mononuclear cell cocultures

• Published in: The Journal of immunology (1950) Vol. 149; no. 2; pp. 676 - 680
• Main Authors: Peterson, PK, Gekker, G, Chao, CC, Schut, R, Verhoef, J, Edelman, CK, Erice, A, Balfour, HH, Jr
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.07.1992; American Association of Immunologists
• Subjects: AIDS/HIV; Biological and medical sciences; Cells, Cultured; Cocaine - pharmacology; Cytomegalovirus - physiology; Fundamental and applied biological sciences. Psychology; HIV-1 - drug effects; HIV-1 - physiology; human immunodeficiency virus 1; Humans; Leukocytes, Mononuclear - microbiology; Microbiology; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Transforming Growth Factor beta - physiology; Tumor Necrosis Factor-alpha - physiology; Virology; Virus Replication - drug effects; Cell culture; Cytomegalovirus; HIV-1 virus; Herpesviridae; Transforming growth factor; Cytokine; Retroviridae; Stimulation; Betaherpesvirinae; Host virus relation; Mechanism; Virus; Lentivirinae; Replication; Cocaine; Human immunodeficiency virus; Infected cell; Tumor necrosis factor α
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.149.2.676

Cocaine and CMV each have been suggested to promote the progression of HIV-1 infection. In the present study, the interaction of cocaine and CMV was investigated in a PBMC coculture assay in which release of HIV-1 p24 Ag into coculture supernatants was used as an index of HIV-1 replication. CMV was an effective activation signal for HIV-1 replication when PBMC from CMV-seropositive donors were used in the coculture assay, and cocaine markedly increased replication of HIV-1 in these cocultures. The synergistic activity of cocaine was reduced by neutralizing antibodies to TNF-alpha and by pentoxifylline, an inhibitor of TNF-alpha mRNA production. Also, antibodies to transforming growth factor-beta (TGF-beta) eliminated the amplifying effect of cocaine on HIV-1 replication, whereas antibodies to IL-6 were inactive. The potentiating effect of cocaine could be reproduced by addition of rTNF-alpha or rTGF-beta to the cocultures of CMV-activated PBMC, although TGF-beta was substantially more potent than TNF-alpha. The possibility that TNF-alpha may act indirectly through stimulation of TGF-beta was suggested by the finding of reduced TGF-beta levels in culture supernatants of PBMC that were treated with CMV and cocaine in the presence of antibodies to TNF-alpha. Thus, cocaine amplifies HIV-1 replication in cocultures containing CMV-activated PBMC via a mechanism that appears to involve both TNF-alpha and TGF-beta. The results of this study support the possibility that cocaine and CMV could enhance HIV-1 replication and, thus, aggravate HIV-1-related disease.