title: The Selective Serotonin Reuptake Inhibitor Citalopram Decreases Human Immunodeficiency Virus Receptor and Coreceptor Expression in Immune Cells.
abstract: This study investigated whether the selective serotonin reuptake inhibitor (SSRI) citalopram downregulates the expression of the human immunodeficiency virus (HIV) receptor cluster of differentiation 4 (CD4) and coreceptors chemokine receptor type 5 and chemokine-related receptor type 4 (CCR5 and CXCR4) on peripheral blood mononuclear cells (PBMCs) and macrophages ex vivo as a potential mechanism of reducing susceptibility to HIV infection.
  
  
  
  The sample included 150 participants 18-58 years old (59% women, 65% African American, 61% with depression). Monocyte-depleted PBMCs were treated with phytohemagglutinin for 72 hours and then cultured in the presence of interleukin-2 with vehicle control or the SSRI (10(-6) mol/L) for 2 hours. To generate monocyte-derived macrophages, monocytes were cultured for 7 days, after which either vehicle control or SSRI (10(-6) mol/L) was added for 2 hours. RNA was collected from both cell types, and messenger RNA expression of CD4, CCR5, and CXCR4 was measured by real-time polymerase chain reaction.
  
  
  
  In PBMCs, SSRI treatment decreased expression of CD4 (p = .009), CCR5 (p = .008), and CXCR4 (p < .0001). In monocyte-derived macrophages, SSRI treatment decreased expression of CD4 (p < .0001) and CXCR4 (p = .0003), but not CCR5 (p = .71). The suppressive effects of the SSRI on receptor expression did not differ as a function of depression diagnosis or depressive symptom severity.
  
  
  
  Treatment with the SSRI at a physiologic dose decreased CD4, CCR5, and CXCR4 expression on PBMCs and macrophages ex vivo. These findings suggest that SSRI treatment, independent of depression status, downregulates HIV receptor and coreceptor expression and may reduce susceptibility of immune cells to HIV infection and decrease inflammation. If clinical trials confirm the present findings, ultimately there may be a role for using SSRI treatment adjunctively in HIV and acquired immunodeficiency syndrome.
authors.affiliation: Departments of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Greeson
authors.affiliation: Departments of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: David R
authors.initials: DR
authors.lastname: Gettes
authors.affiliation: Division of Allergy and Immunology, The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania.
authors.forename: Sergei
authors.initials: S
authors.lastname: Spitsin
authors.affiliation: Departments of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Benoit
authors.initials: B
authors.lastname: Dubé
authors.affiliation: Departments of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Child and Adolescent Psychiatry and Behavioral Science, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Tami D
authors.initials: TD
authors.lastname: Benton
authors.affiliation: Departments of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Lynch
authors.affiliation: Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Allergy and Immunology, The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Douglas
authors.affiliation: Departments of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania; Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: dlevans@mail.med.upenn.edu.
authors.forename: Dwight L
authors.initials: DL
authors.lastname: Evans
mesh_terms: D000293:Adolescent; D000328:Adult; D015704:CD4 Antigens / Q000187:drug effects*; D015283:Citalopram / Q000494:pharmacology*; D003866:Depressive Disorder / Q000188:drug therapy*; D015536:Down-Regulation; D005260:Female; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D019713:Receptors, CCR5 / Q000187:drug effects*; D019718:Receptors, CXCR4 / Q000187:drug effects*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D015704:CD4 Antigens; D015283:Citalopram; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D017367:Selective Serotonin Reuptake Inhibitors; C584933:CCR5 protein, human; C527276:CXCR4 protein, human
keywords: CCR5; CD4; CXCR4; Depression; HIV; SSRI