Differential effect of the immunomodulatory hormone somatostatin on replication of human immunodeficiency virus type 1 in CD4+ and CD8+ T lymphocytes.
The long-acting somatostatin analog octreotide (SMS 201-995) possesses immunosuppressive properties and has been successfully used for the management of human immunodeficiency virus (HIV)-associated diarrhea, a condition commonly observed in the absence of known enteric pathogens. Since HIV type 1 (HIV-1) replication can occur in both CD4+ and CD8+ lymphocytes, we hypothesized that this benefit might be due to local effects on HIV-1 replication in these two T-cell subsets. As a model, we studied the effects of two synthetic molecules, SRIH 1-14 and SRIH 1-28, closely related to naturally occurring forms of somatostatin, as well as SMS 201-995 on HIV-1 replication in CD4+ and CD8+ cells derived from peripheral blood mononuclear cells (PBMC). We found that HIV-1 replication was inhibited in CD8+ cells but enhanced in infected CD4+ lymphocytes, as measured by p24 antigen levels in culture fluids. These differential effects were drug concentration dependent. We also observed that somatostatin inhibited the mitogen-induced proliferative responsiveness of both cell types. These effects on both HIV-1 replication and cell proliferation were independent of somatostatin gene expression, since somatostatin mRNAs were not detected in mitogen-stimulated PBMC, as determined by reverse transcription-PCR.
Mercure
L
L
Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.
Phaneuf
D
D
Wainberg
M A
MA
D001483:Base Sequence; D016516:CD4-CD8 Ratio / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology*; D002478:Cells, Cultured; D015870:Gene Expression; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D015282:Octreotide / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013004:Somatostatin / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D013268:Stimulation, Chemical; D014158:Transcription, Genetic; D014779:Virus Replication / Q000187:drug effects*
D010835:Phytohemagglutinins; D012333:RNA, Messenger; D013004:Somatostatin; D015282:Octreotide