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From the Department of Infectious Diseases, University La Sapienza,
Rome, Italy; the Department of Experimental Medicine, University of
L'Aquila, L'Aquila, Italy; Centro Medico di San Patrignano, Rimini,
Italy; and the National Cancer Institute, National Institutes of
Health, Bethesda, MD.
The Fas/Fas ligand system is involved in uncontrolled apoptosis,
which ultimately leads to the loss of T lymphocytes in human immunodeficiency virus (HIV)-infected individuals. The signal transduced by Fas receptor involves the activation of an acidic sphingomyelinase, sphingomyelin breakdown, and ceramide production. Our
recent reports have shown that L-carnitine inhibits Fas-induced apoptosis and ceramide production both in vitro and in vivo. The aim of
this study was to study, in a preliminary fashion, the impact of
long-term L-carnitine administration on CD4 and CD8 absolute counts,
rate, and apoptosis in HIV-1-infected subjects. The generation of
cell-associated ceramide and HIV-1 viremia was also investigated.
Eleven, asymptomatic, HIV-1-infected subjects, who refused any
antiretroviral treatment despite experiencing a progressive decline of
CD4 counts, were treated with daily infusions of L-carnitine (6 g) for
4 months. Immunologic and virologic measures and safety were monitored
at the start of the treatment and then on days 15, 30, 90, and 150. L-carnitine therapy resulted in an increase of absolute CD4 counts,
which was statistically significant on day 90 and 150 (P = .010 and P = .019, respectively). A positive, not significant
trend was also observed even in the change in absolute counts of CD8
lymphocytes. L-carnitine therapy also led to a drop in the frequency of
apoptotic CD4 and CD8 lymphocytes. This reduction occurred gradually,
but changes in actual values between each time point and baseline were
strongly significant (P = .001 at the end of the study
compared with the baseline). A strong reduction (P = .001) in
cell-associated ceramide levels was found at the end of the study. In
general, HIV-1 viremia increased slightly. No toxicity related to
L-carnitine therapy was observed and dose reductions were not
necessary. In HIV-1-infected subjects, long-term infusions of
L-carnitine produced substantial increases in the rate and absolute
counts of CD4 and, to a lesser degree, of CD8 lymphocytes. This was
paralleled by a reduced frequency of apoptotic cells of both subgroups
and a decline in the levels of ceramide. No clinically relevant change
of HIV-1 viremia was observed.
Blood, Vol. 91 No. 10 (May 15), 1998:
pp. 3817-3824
This article has been cited by other articles:
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| Copyright © 1998 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
