TY - JOUR
T1 - The selective serotonin reuptake inhibitor citalopram decreases human immunodeficiency virus receptor and coreceptor expression in immune cells
AU - Greeson, Jeffrey M.
AU - Gettes, David R.
AU - Spitsin, Sergei
AU - Dubé, Benoit
AU - Benton, Tami D.
AU - Lynch, Kevin G.
AU - Douglas, Steven D.
AU - Evans, Dwight L.
N1 - Funding Information:
This work was supported by the National Institutes of Health (NIH) Grant No. R01MH082670 (Principal Investigator: DLE). This publication was made possible through support from the Penn Mental Health AIDS Research Center, funded by NIH Grant No. P30MH097488 (Principal Investigator: DLE). The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official view of the NIH.
Publisher Copyright:
© 2016 Society of Biological Psychiatry.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - Background 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. Methods 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. Results 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. Conclusions 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.
AB - Background 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. Methods 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. Results 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. Conclusions 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.
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U2 - 10.1016/j.biopsych.2015.11.003
DO - 10.1016/j.biopsych.2015.11.003
M3 - Article
C2 - 26725193
AN - SCOPUS:84951851495
SN - 0006-3223
VL - 80
SP - 33
EP - 39
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 1
ER -