Differential effect of the immunomodulatory hormone somatostatin on replication of human immunodeficiency virus type 1 in CD4+ and CD8+ T lymphocytes.

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

Differential effect of the immunomodulatory hormone somatostatin on replication of human immunodeficiency virus type 1 in CD4+ and CD8+ T lymphocytes.

Clin Diagn Lab Immunol. 1995 Mar;2(2):192-8. Unique Identifier : AIDSLINE MED/95211634
Mercure L; Phaneuf D; Wainberg MA; Lady Davis Institute, Jewish General Hospital, Montreal, Quebec,; Canada.

Abstract: 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.

Keywords: Base Sequence Cells, Cultured Comparative Study CD4-CD8 Ratio/DRUG EFFECTS CD4-Positive T-Lymphocytes/*DRUG EFFECTS/IMMUNOLOGY/*VIROLOGY CD8-Positive T-Lymphocytes/*DRUG EFFECTS/IMMUNOLOGY/*VIROLOGY Gene Expression Human HIV-1/*DRUG EFFECTS/*PHYSIOLOGY Leukocytes, Mononuclear/DRUG EFFECTS/METABOLISM Lymphocyte Transformation/DRUG EFFECTS Molecular Sequence Data Octreotide/PHARMACOLOGY Phytohemagglutinins/ANTAGONISTS & INHIB/PHARMACOLOGY RNA, Messenger/BIOSYNTHESIS/GENETICS Somatostatin/BIOSYNTHESIS/GENETICS/*PHARMACOLOGY Stimulation, Chemical Support, Non-U.S. Gov't Transcription, Genetic Virus Replication/*DRUG EFFECTS JOURNAL ARTICLE
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M9570899

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