Cardiopulmonary bypass produces greater pulmonary than systemic proinflammatory cytokines.
Cardiopulmonary bypass (CPB) impairs pulmonary endothelial injury in part by increasing expression of adhesion molecules that results in neutrophil influx. Although numerous proinflammatory cytokines up-regulate these responses, the extent to which systemic and pulmonary proinflammatory cytokines increase remains unknown. We therefore examined systemic and pulmonary gene expression and production of proinflammatory cytokines during CPB. Bronchoalveolar lavage and peripheral blood sampling were performed just after the induction of anesthesia and at the end of surgery in 80 patients undergoing CPB. RNA was extracted from harvested cells and cDNA was synthesized by reverse transcription. The expression of interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) was measured by semiquantitative polymerase chain reaction using beta-actin as an internal standard. We also measured these cytokines in cultured alveolar macrophages and plasma monocytes in standard medium alone, or in the presence of lipopolysaccharide. We found 2- to 20-fold increases in gene expression for these cytokines in both plasma and alveolar leukocytes at the end of surgery. However, the increases were 4-8 times greater in alveolar than plasma leukocytes. Alveolar macrophages obtained at the end of surgery produced 1.5-3 times more IL-6, IL-8, and TNF-alpha than those obtained at the beginning (P < 0.0001). Although plasma monocytes produced more IL-8 at the end of surgery (P < 0.001), TNF-alpha and IL-6 did not increase. The production of all cytokines was 1.5-3 times greater in alveolar macrophages obtained at the end of surgery than in plasma monocytes obtained simultaneously (P < 0.005). Our data thus suggest that CPB provokes a greater pulmonary than systemic inflammatory response.
Kotani
N
N
Department of Anesthesiology, University of Hirosaki School of Medicine, Hirosaki, Japan. nao@cc.hirosaki-u.ac.jp
Hashimoto
H
H
Sessler
D I
DI
Muraoka
M
M
Wang
J S
JS
O'Connor
M F
MF
Matsuki
A
A
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002315:Cardiopulmonary Bypass; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D000199:Actins; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D012313:RNA