Selective Serotonin Reuptake Inhibitor and Substance P Antagonist Enhancement of Natural Killer Cell Innate Immunity in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome
Received 26 February 2007; received in revised form 6 July 2007; accepted 15 August 2007. published online 18 October 2007.
Background
Natural killer (NK) cells play an important role in innate immunity and are involved in the host defense against human immunodeficiency virus (HIV) infection. This study examines the potential role of three underlying regulatory systems that have been under investigation in central nervous system research as well as immune and viral research: serotonin, neurokinin, and glucocorticoid systems.
Methods
Fifty-one HIV-seropositive subjects were recruited to achieve a representative sample of depressed and nondepressed women. The effects of a selective serotonin reuptake inhibitor (SSRI), a substance P (SP) antagonist, and a glucocorticoid antagonist on NK cell function were assessed in a series of ex vivo experiments of peripheral blood mononuclear cells from each HIV-seropositive subject.
Results
Natural killer cell cytolytic activity was significantly increased by the SSRI citalopram and by the substance P antagonist CP-96345 relative to control conditions; the glucocorticoid antagonist, RU486, showed no effect on NK cytotoxicity. Our results suggest that the effects of the three agents did not differ as a function of depression.
Conclusions
Our findings provide evidence that NK cell function in HIV infection may be enhanced by serotonin reuptake inhibition and by substance P antagonism. It remains to be determined if HIV-related impairment in not only NK cytolytic activity but also NK noncytolytic activity can be improved by an SSRI or an SP antagonist. Clinical studies are warranted to address these questions and the potential roles of serotonergic agents and SP antagonists in improving NK cell immunity, delaying HIV disease progression, and extending survival with HIV infection.
aDepartment of Psychiatry, Joseph J. Stokes Research Institute of The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
bDepartment of Medicine, Joseph J. Stokes Research Institute of The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
cDepartment of Neuroscience, Joseph J. Stokes Research Institute of The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
dDivision of Allergy and Immunology, Joseph J. Stokes Research Institute of The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
eDivision of Allergy and Immunology, Joseph J. Stokes Research Institute of The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
fDepartment of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Address reprint requests to Dwight L. Evans, M.D., Ruth Meltzer Professor and Chairman, Department of Psychiatry, University of Pennsylvania School of Medicine, 305 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104
ABSTRACT