Mitochondria alterations and dramatic tendency to undergo apoptosis in peripheral blood lymphocytes during acute HIV syndrome.
OBJECTIVE
To study alterations of mitochondrial membrane potential (delta psi) and the propensity to undergo apoptosis in peripheral blood lymphocytes (PBL) from subjects with acute HIV syndrome; and to evaluate 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 freshly collected PBL from patients with symptomatic, acute HIV-1 primary infection, which were cultured for different durations in the presence of absence of NAC. NAM or LAC. By a cytofluorimetric method allowing analysis of delta psi in intact cells, we studied the function of these organelles under the different conditions. PBL apoptosis was evaluated by the classic cytofluorimetric method of propidium iodide staining, capable of revealing the typical DNA hypodiploid peak.


RESULTS
Significant delta psi alterations and tendency to undergo apoptosis were present in PBL from the subjects we studied. Indeed, when cultured even for a few hours in the absence of any stimulus, a consistent number of cells died. However, the presence of even different levels of NAC, NAM 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 earliest phases of the syndrome (before seroconversion), and changed significantly after a few days. A significant correlation was found between spontaneous apoptosis and tumour necrosis factor (TNF)-alpha or p24 plasma levels, as well as between apoptosis and the percentages of circulating CD4+ or CD8+ T cells.


CONCLUSIONS
PBL from patients with acute HIV syndrome are characterized by both significant mitochondrial alterations and a dramatic tendency to undergo apoptosis. The use of NAC, NAM or LAC seems to rescue cells through a protective effect on mitochondria, a well-known target for the action of TNF-alpha and for reactive oxygen species, the production of which is strongly induced by this cytokine. Thus, our data could provide the rationale for the use of such agents in addition to antiviral drugs in primary infection.
Cossarizza
A
A
Department of Biomedical Sciences, University of Modena School of Medicine, Italy.
Mussini
C
C
Mongiardo
N
N
Borghi
V
V
Sabbatini
A
A
De Rienzo
B
B
Franceschi
C
C
D000108:Acetylcarnitine / Q000494:pharmacology; D000111:Acetylcysteine / Q000494:pharmacology; D000208:Acute Disease; D000328:Adult; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes; D002478:Cells, Cultured; D005260:Female; D016655:HIV Core Protein p24 / Q000097:blood; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007425:Intracellular Membranes; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D008564:Membrane Potentials; D008928:Mitochondria / Q000502:physiology*; D009536:Niacinamide / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000975:Antioxidants; D016655:HIV Core Protein p24; D014409:Tumor Necrosis Factor-alpha; D009536:Niacinamide; D000108:Acetylcarnitine; D000111:Acetylcysteine