Effect of l-carnitine treatment in vivo on apoptosis and ceramide generation in peripheral blood lymphocytes from aids patients: correlation with in vitro results

In the present study, the effects of a short-term (5 days) endovenous treatment with L-carnitine (6 g/die) on apoptosis of CD4 and CDS cells from ten AIDS patients have been examined. L-carnitine administration has been shown to strongly induce a reduction of the percentage of cells undergoing apoptosis which was paralleled with a significant increase of CD4 and CDS cells. Interestingly, L-carnitine treatment, which did not show relevant side-effects in our patients, led to a strong and significant reduction of PBMCassociated ceramide, an intracellular messenger for apoptosis, that correlated with the decrease of apoptotic CD4 and CDS positive cells. These results suggest that L-carnitine could be an effective anti-apoptotic drug in AIDS patients. In vitro studies were also performed to better characterize the effects of carnitine on cell apoptosis. A high expression of Fas/Fas ligand system in PBMC from HIV-positive individuals has been previously reported and could be responsible for the observed relevant apoptosis of both infected and uninfected cells. Thus, we investigated the effects of L-carnitine in vitro on apoptosis- and ceramide generation-induced by Fas crosslinking through an anti-Fas mAb in Fas-sensitive cell lines (HuT78 and U937) and the results strongly support the in vivo observations.