MITOCHONDRIA ALTERATIONS AND DRAMATIC TENDENCY TO UNDERGO APOPTOSIS IN PERIPHERAL-BLOOD LYMPHOCYTES DURING ACUTE HIV SYNDROME

Objective: To study alterations of mitochondrial membrane potential (D elta psi) and the propensity to undergo apoptosis in peripheral blood lymphocytes (PBL) from subjects with acute HIV syndrome; and to evalua te possible modulations of these phenomena by antioxidants that can be used in therapy, such as N-acetyl-cysteine (NAC), nicotinamide (NAM), or L-acetyl-carnitine (LAC). Methods: Mitochondrial function and the tendency of PBL to undergo spontaneous apoptosis were studied on fresh ly collected PBL from patients with symptomatic, acute HIV-1 primary i nfection, which were cultured for different durations in the presence or absence of NAG, NAM or LAG. By a cytofluorimetric method allowing a nalysis of Delta psi in intact cells, we studied the function of these organelles under the different conditions. PBL apoptosis was evaluate d by the classic cytofluorimetric tnethod of propidium iodide staining , capable of revealing the typical DNA hypodiploid peak. Results: Sign ificant Delta psi alterations and tendency to undergo apoptosis were p resent in PBL from the subjects we studied. Indeed, when cultured even for a few hours in the absence of any stimulus, a consistent number o f cells died. However, the presence of even different levels of NAG, N AM or LAC was able to rescue most of them from apoptosis. Both a fall in Delta psi and apoptosis were evident in PBL collected in the earlie st phases of the syndrome (before seroconversion), and changed signifi cantly after a few days. A significant correlation was found between s pontaneous apoptosis and tumour necrosis factor (TNF)-alpha or p24 pla sma levels, as well as between apoptosis and the percentages of circul ating CD4+ or CD8+ T cells. Conclusions: PBL from patients with acute HIV syndrome are characterized by both significant mitochondrial alter ations and a dramatic tendency to undergo apoptosis. The use of NAC, N AM or LAC seems to rescue cells through a protective effect on mitocho ndria, a well-known target for the action of TNF-alpha and for reactiv e oxygen species, the production of which is strongly induced by this cytokine. Thus, our data could provide the rationale for the use of su ch agents in addition to antiviral drugs in primary infection.