Cocaine amplifies HIV-1 replication in cytomegalovirus-stimulated peripheral blood mononuclear cell cocultures.
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.
Peterson
P K
PK
Department of Medicine, Hennepin County Medical Center, Minneapolis, MN 55415.
Gekker
G
G
Chao
C C
CC
Schut
R
R
Verhoef
J
J
Edelman
C K
CK
Erice
A
A
Balfour
H H
HH
D002478:Cells, Cultured; D003042:Cocaine / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000502:physiology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000382:microbiology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects*
D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D003042:Cocaine