Ceramide, AIDS and long-term survivors

Acetyl-l-carnitine Administration Increases Insulin-like Growth Factor 1 Levels in Asymptomatic HIV-1-Infected Subjects: Correlation with Its Suppressive Effect on Lymphocyte Apoptosis and Ceramide Generation

“…The PBMC-associated ceramide levels were significantly higher at baseline (42 Ϯ 6.28 pmol/10 6 cells) in the patient group in comparison to healthy individuals (10.2 Ϯ 2.3 pmol/10 6 cells), in accordance with our previous work (11,12,(43)(44)(45). Acetyl-L-carnitine therapy led to a progressive decline in the ceramide levels with respect to the baseline (Fig.…”

“…Recent work from our laboratory (10) has demonstrated that carnitines interfere with Fas-transduced apoptotic signaling through down-regulating the production of ceramide, an endogenous mediator of apoptosis (47-51), which appears to be involved in inappropriate HIV-infection-associated apoptosis (43,44). The finding that acetyl-L-carnitine therapy of asymptomatic HIV-infected patients significantly reduced both the frequency of apoptotic CD4 lymphocytes and the levels of lymphocyte-associated ceramide adds weight to previous studies and suggests the potential for L-carnitine therapy to slow the progression of HIV-1 infection through reducing the apoptotic loss of lymphoid cells.…”

Ceramide Involvement in Apoptosis and Apoptotic Diseases

“…In general, HIV-1-infected individuals develop AIDS within several years, but about 5% remain healthy over an extended time (and are known as long-term nonprogressors) [68]. Interestingly, De Simone and coworkers observed that HIV-1-infected long-term nonprogressors have less elevated lymphocyte-associated Cer levels than subjects with evolving disease [66,69,70]. Remarkably, this is paralleled by a lower frequency of apoptotic CD4 and CD8 cells in long-term nonprogressors than in patients with AIDS.…”

Current Status and Perspectives in Ceramide-Targeting Molecular Medicine

“…An increase of ceramide was reported in HIVinfected cells in vitro [107] and in vivo [108]. Furthermore, the level of ceramide in peripheral blood lymphocytes was significantly lower in HIV-infected long-term survivors than in AIDS patients, suggesting a role for ceramide in pathogenesis of HIV infection [108]. A pilot study showed reduction of ceramide levels concomitant with reduction of apoptotic T lymphocytes in HIV-infected patients treated with L-carnitine [109].…”