[Proapoptotic effect of propofol on T cells].
BACKGROUND
Surgery and general anesthesia induce excessive apoptosis on peripheral lymphocytes and this phenomenon significantly contributes to the postoperative lymphocytopenia. However, the role played by anesthetic agents on this event remains to be elucidated. In this study we examined whether an anesthetic compound such as propofol is able to exert, in vitro, a proapoptotic effect on T cells.


METHODS
Lymphocytes were isolated from heparinized venous blood in healthy volunteers and were incubated with propofol at clinically relevant concentration (5 mg/ml) and at 10 times this concentration (50 mg/ml). The counts of cells either bearing the Fas/FasL phenotype or expressing the intracellular Bcl2 protein were determined by means of flow cytometry. Assessment of lymphocytes undergoing apoptosis was made both by staining of apoptotic nuclei with propidium iodide (PI) and by phenotypic analysis of apoptotic cells with 7-amino-actinomycin D (7-AAD).


RESULTS
Treated lymphocytes exhibit a significantly enhanced expression of Fas/FssL system associated with a decrease of Bcl2 expression at both 5 and 50 mg/ml propofol concentrations (p<0.05). On the other hand, the rate of apoptotic cells was not significantly different as compared to control in the absence of propofol.


CONCLUSIONS
Propofol impairs, in vitro, both Fas/FasL and Bcl2 expressions on lymphocytes at clinically relevant concentrations but fails to induce apoptotic cell death. It is suggested that the antioxidative properties of the drug could inhibit some way the mechanisms by which mitochondrial free-radicals mediating apoptosis ultimately lead to cell death execution.
Delogu
G
G
Istituto di Anestesia e Rianimazione, Università degli Studi La Sapienza, Rome, Italy.
Marandola
M
M
Tellan
G
G
Moretti
S
S
Marcellini
S
S
Iacoella
C
C
Rizzitano
D
D
Signore
L
L
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers; D053222:Fas Ligand Protein; D006801:Humans; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000097:blood; D015742:Propofol / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects*
D018686:Anesthetics, Intravenous; D015415:Biomarkers; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015742:Propofol