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Selective serotonin reuptake inhibitor and substance P antagonist enhancement of natural killer cell innate immunity in human immunodeficiency virus/acquired immunodeficiency syndrome.

Evans DL, Lynch KG, Benton T, Dubé B, Gettes DR, Tustin NB, Lai JP, Metzger D, Douglas SD

Department of Psychiatry, Joseph J. Stokes Research Institute of The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. psych@mail.med.upenn.edu

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.

Published 8 April 2008 in Biol Psychiatry, 63(9): 899-905.
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Articles on AIDS published 25 March 2008:

Nevirapine-induced Stevens-Johnson syndrome in an HIV patient.   Cornea, 27(3): 366-7.

PURPOSE: To report a case of nevirapine-induced Stevens-Johnson syndrome (SJS) misdiagnosed as viral keratitis. METHODS: A 35-year-old AIDS patient, on antiretroviral therapy (ART) with stavudine, nevirapine, and lamivudine, developed bilateral ocular congestion and irritation. He was being treated elsewhere for bilateral herpetic epithelial keratitis. On progressive worsening of symptoms, he presented with complaints of severe photophobia and foreign-body sensation in both eyes. RESULTS: The ... [Abstract] [Full-text]

Articles on AIDS published 12 March 2008:

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Articles on AIDS published 11 March 2008:

Utilization of mental health and substance abuse care for people living with HIV/AIDS, chronic mental illness, and substance abuse disorders.   J Acquir Immune Defic Syndr, 47(4): 449-58.

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Articles on AIDS published 3 March 2008:

Phase 1/2 trial of BMS-275291 in patients with human immunodeficiency virus-related Kaposi sarcoma: a multicenter trial of the AIDS Malignancy Consortium.   Cancer, 112(5): 1083-8.

BACKGROUND: Matrix metalloproteinases (MMPs) are overexpressed in Kaposi sarcoma (KS). The safety and efficacy of a novel, orally bioavailable MMP inhibitor, BMS-275291, was evaluated in patients with human immunodeficiency virus-associated KS and the correlation between changes in the percentage of apoptotic cells in tumor biopsies and response was explored. METHODS: Cohorts of 6 patients were to be treated with BMS-275291. The initial cohort received 1200 mg once a day; subsequent doses were ... [Abstract] [Full-text]

Articles on AIDS published 28 February 2008:

Adverse drug reactions in adult medical inpatients in a South African hospital serving a community with a high HIV/AIDS prevalence: prospective observational study.   Br J Clin Pharmacol, 65(3): 396-406.

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Articles on AIDS published 25 February 2008:

Successful treatment with modified CHOP-rituximab in pediatric AIDS-related advanced stage Burkitt lymphoma.   Pediatr Blood Cancer, 50(4): 883-5.

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Articles on AIDS published 19 February 2008:

AIDS and ophthalmology: the first quarter century.   Am J Ophthalmol, 145(3): 397-408.

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