Effect of L-Carnitine on Human Immunodeficiency Virus-1 Infection-Associated Apoptosis: A Pilot Study

Abstract

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.

A Prospective, Double Blind, Randomised, Placebo Controlled Trial Evaluating Acetyl-L-Carnitine (ALCAR) for the Prevention of Distal Symmetric Polyneuropathy in HIV Infected Individuals

“…A small Italian trial treated 11 HIV / hepatitis C co-infected patients with ALCAR but not with a standard antiretroviral regime. Under these conditions a significant rise of CD4 cell counts was noted after 4 months [24]. In our study, we could not confirm either a virological or an immunological benefit of ALCAR over 48 weeks compared to placebo.…”

“…This effect may have been due to a reduced frequency of apoptosis of CD4 and CD8 cells associated with ALCAR administration [2,6,21]. ALCAR has also been suggested as a potential therapy for HIV-related lipodystrophy and metabolic syndrome [22][23][24].…”

Effects of calf thymus extract and L-carnitine on immunity and growth performance of broiler chickens

“…28 Regarding the role of L-carnitine in cellular immunity, it was present in lymphocytes at high concentrations, and inhibited apoptosis of those immune cells, there was a very significant increase in number of lymphocytes in CTE treated groups, when compared to other groups. 29 In regardes to relative Bursa of Fabricious and spleen weights were significantly increased than control, this referred to increase lymphocyte cell%. 27 that due to decrease the total number of thymocytes and splenocytes by the effect of stress which is also accompanied by decreasing weight ratio of the spleen.…”

Effects of dietary taurine, carnitine and cholesterol supplementation on growth performance and immunological status ofLitopenaeus vannameiunder cold exposure

“…Dietary carnitine of 0.012% (Table ) also seemed to help strengthen the haemocyte immunity of shrimp in this study, though little is known about carnitine requirement of shrimp. Carnitine is reported to inhibit apoptosis of lymphocytes (Famularo & Simone ; Moretti, Alesse, Di Marzio, Zazzeroni, Ruggeri, Marcellini, Famularo, Steinberg, Boschini, Cifone & De Simone ) and enhanced the pro‐liferative response of lymphocytes to mitogens (De Simone, Famularo, Tzantzoglou, Trinchieri, Moretti & Sorice ), but the mode of immunomodulation by carnitine is not clear. The modified metabolism of lipids (LaCount, Drackley & Weigel ) and enhanced secretion of hormones, such as insulin, insulin‐like growth factor‐I (Musser, Goodband, Tokach, Owen, Nelssen, Blum, Campbell, Smits & Civis ) and triiodothyronine (T3) (Buyse, Janssens & Decuypere ) may be involved in mammals, but less is known about the modulation process of carnitine in crustaceans.…”