Inhalation anesthetics induce apoptosis in normal peripheral lymphocytes in vitro.
BACKGROUND
The authors hypothesized that perioperative lymphocytopenia is partially caused by apoptosis of lymphocytes induced by inhalation anesthetics. Therefore, they evaluated whether sevoflurane and isoflurane induce apoptosis of normal peripheral lymphocytes.


METHODS
Normal peripheral blood mononuclear cells were exposed to sevoflurane and isoflurane, and the percentages of apoptotic lymphocytes was measured by Annexin V-fluorescein isothiocyanate-7-amino actinomycin D flow cytometry after 24 h of exposure (0.5, 1.0, and 1.5 mm) and after 6, 12, and 24 h of exposure (1.5 mm). The percentages of lymphocytes with caspase 3-like activity were also measured after 24 h of exposure (1.5 mm).


RESULTS
The percentages of apoptotic lymhocytes were increased in a dose-dependent manner (controls: 5.1 +/- 1.4%; sevoflurane: 7.3 +/- 1.3% [0.5 mm], 9.1 +/- 1.5% [1.0 mm], 12.6 +/- 2.1% [1.5 mm]; isoflurane: 7.5 +/- 1.6% [0.5 mm], 10.5 +/- 1.5% [1.0 mm], 16.3 +/- 2.7% [1.5 mm]) after 24 h of exposure and in a time-dependent manner (controls: 1.2 +/- 0.4% [6 h], 3.4 +/- 0.7% [12 h], 5.6 +/- 1.2% [24 h]; sevoflurane: 1.8 +/- 0.4% [6 h], 6.4 +/- 1.2% [12 h], 11.3 +/- 2.2% [24 h]; isoflurane: 2.6 +/- 0.5% [6 h], 8.8 +/- 1.5% [12 h],16.0 +/- 1.9% [24 h]) at the concentration of 1.5 mm. The percentages of lymphocytes with caspase 3-like activity were increased (controls: 10.0 +/- 1.1%; sevoflurane: 13.8 +/- 1.2%; isoflurane: 17.0 +/- 1.3%).


CONCLUSIONS
Both sevoflurane and isoflurane induced apoptosis in peripheral lymphocytes in dose-dependent and time-dependent manners in vitro.
Matsuoka
H
H
Department of Anesthesiology, Tohoku University School of Medicine, Sendai, Miyagi, Japan. h_matsuoka@aries.biglobe.ne.jp
Kurosawa
S
S
Horinouchi
T
T
Kato
M
M
Hashimoto
Y
Y
D000328:Adult; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D017302:Annexins; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004396:Coloring Agents; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D017302:Annexins; D004396:Coloring Agents; D008738:Methyl Ethers; D000077149:Sevoflurane; D007530:Isoflurane; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases