Effect of L-carnitine on human immunodeficiency virus-1 infection-associated apoptosis: a pilot study.
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.
Moretti
S
S
Department of Infectious Diseases, University La Sapienza, Rome, Italy.
Alesse
E
E
Di Marzio
L
L
Zazzeroni
F
F
Ruggeri
B
B
Marcellini
S
S
Famularo
G
G
Steinberg
S M
SM
Boschini
A
A
Cifone
M G
MG
De Simone
C
C
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002331:Carnitine / Q000494:pharmacology* / Q000627:therapeutic use; D002518:Ceramides / Q000096:biosynthesis; D053222:Fas Ligand Protein; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015497:HIV-1; D006801:Humans; D018655:Lymphocyte Count / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects* / Q000502:physiology; D010865:Pilot Projects; D012449:Safety; D015398:Signal Transduction / Q000187:drug effects; D015819:Substance Abuse, Intravenous / Q000150:complications; D016896:Treatment Outcome; D014766:Viremia / Q000188:drug therapy* / Q000473:pathology; D019014:fas Receptor / Q000502:physiology*
D002518:Ceramides; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D002331:Carnitine