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1996-02-26
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Document 0202
DOCN M9620202
TI Cyclosporine-induced apoptosis in CD4+ T lymphocytes and
computer-simulated analysis: modeling a treatment scenario for HIV
infection.
DT 9602
AU Huss R; Hoy CA; Ottinger H; Grosse-Wilde H; Deeg HJ; Clinical Research
Division, Fred Hutchinson Cancer Research; Center, Seattle, WA, USA.
SO Res Immunol. 1995 Feb;146(2):101-8. Unique Identifier : AIDSLINE
MED/96100666
AB Cyclosporine A (CsA) is a potent immunosuppressive drug which interferes
in vitro and in vivo with T-cell function. CsA has been shown to arrest
T-cell maturation intrathymically and to inhibit T-cell proliferation.
In this study, we demonstrate that CsA induces apoptosis in the canine
CD4+ CD8- T-lymphocyte cell line 401 in a dose- and time-dependent
fashion. Similar results could also be obtained from human peripheral
blood lymphocytes. Apoptosis is observed within 4 hours after CsA
application and is not prevented by excessive addition of ConA
supernatant as a source of interleukins. The induction of apoptosis in
CD4+ T lymphocytes suggests a possible treatment option for human
immunodeficiency virus (HIV) infections, since the major target
population for the HIV would be ablated at short term. A
computer-simulated analysis with the Cybermouse HIV model confirmed that
the virus would eventually disappear and HIV-infected macrophages would
also be substantially reduced if CsA were given in combination with
drugs which block viral replication (3'-azido 3'-deoxythymidine or
2',3'-dideoxycytidine). This treatment scenario could be applied under
controlled conditions and with supportive patient care. A further review
of the literature also suggests the positive impact of CsA treatment on
the progression and outcome of AIDS-related mortality.
DE Animal Apoptosis/DRUG EFFECTS/*IMMUNOLOGY Cell Line *Computer
Simulation Cyclosporine/*PHARMACOLOGY CD4-Positive T-Lymphocytes/*DRUG
EFFECTS/IMMUNOLOGY Dogs Growth Inhibitors/PHARMACOLOGY Human HIV
Infections/*DRUG THERAPY Lymphocyte Depletion Lymphocyte
Transformation/DRUG EFFECTS *Models, Biological Support, Non-U.S.
Gov't Support, U.S. Gov't, P.H.S. JOURNAL ARTICLE REVIEW REVIEW OF
REPORTED CASES
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).