Cocaine differentially modulates chemokine production by mononuclear cells from normal donors and human immunodeficiency virus type 1-infected patients.

Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

Cocaine differentially modulates chemokine production by mononuclear cells from normal donors and human immunodeficiency virus type 1-infected patients.

Clin Diagn Lab Immunol. 2000 Jan;7(1):96-100. Unique Identifier : AIDSLINE MED/20087390
Nair MP; Chadha KC; Hewitt RG; Mahajan S; Sweet A; Schwartz SA; State University of New York at Buffalo, Buffalo General; Hospital, Buffalo, New York 14203, USA. mnair@acsu.buffalo.edu

Abstract: Earlier studies have supported a significant role for cocaine in the susceptibility to and the progression of human immunodeficiency virus type 1 (HIV-1) infection. Recently, several unique HIV-1 entry coreceptors (e.g., CCR5 and CCR3) and a trio of HIV-1-specific suppressor chemokines, namely, RANTES (regulated-upon-activation T expressed and secreted), macrophage inflammatory protein 1alpha (MIP-1alpha) and MIP-1beta, were identified. Although cocaine has been linked to the immunopathogenesis of HIV-1 infection, the corresponding cellular and molecular mechanism(s) have not been well defined. We hypothesize that cocaine mediates these pathologic effects through the downregulation of HIV-1-suppressing chemokines and/or upregulating HIV-1 entry coreceptors in HIV-1-infected subjects, resulting in disease progression to AIDS. Our results show that cocaine selectively downregulates endogenous MIP-1beta secretion by normal peripheral blood mononuclear cells (PBMC), while cocaine did not affect the MIP-1beta production by PBMC from AIDS patients. Cocaine also selectively suppresses lipopolysaccharide-induced MIP-1beta production by PBMC from HIV-infected patients. Further, cocaine significantly downregulates endogenous MIP-1beta gene expression, while it upregulates HIV-1 entry coreceptor CCR5 by normal PBMC. These studies suggests a role for cocaine as a cofactor in the pathogenesis of HIV infection and support the premise that cocaine increases susceptibility to and progression of HIV-1 infection by inhibiting the synthesis of HIV-1 protective chemokines and/or upregulating the HIV-1 entry coreceptor, CCR5.

Keywords: JOURNAL ARTICLE Chemokines/*BIOSYNTHESIS Cocaine/*PHARMACOLOGY Down-Regulation (Physiology)/DRUG EFFECTS Human HIV Infections/*METABOLISM *HIV-1 Leukocytes, Mononuclear/DRUG EFFECTS/*METABOLISM Lipopolysaccharides/PHARMACOLOGY Macrophage Inflammatory Protein-1/GENETICS/SECRETION Macrophage Inflammatory Proteins/GENETICS/SECRETION Reverse Transcriptase Polymerase Chain Reaction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S.
000530
A0052193

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