Background: The ability of leukocytes to release proinflammatory cytokines
on lipopolysaccharide stimulation in vitro is impaired after cardiopulmonar
y bypass (CPB). This study tested contribution and interaction of humoral f
actors In altered leukocyte responsiveness to lipopolysaccharide,
Methods: Whole blood and isolated peripheral-blood mononuclear cells (PBMCs
) from 10 patients obtained after induction of anesthesia (T-1) and 20 min
(T-2) and 24 h (T-3) after CPB were cultured in the absence or presence of
lipopolysaccharide and assessed for release of tumor necrosis factor alpha
(TNF-alpha) and interleukin (IL)-1 beta and their functional antagonists, I
L-1 receptor antagonist (IL-1ra) and IL-10. In addition, dose-response char
acteristics and interaction of IL-10 and norepinephrine as modulators of TN
F-alpha release mere studied.
Results: Cardiopulmonary bypass induced release of antiinflammatory (T-2: I
L-10: median 25 pg/ml, 25th-75th percentile 9-42; IL1ra: median 1,528 pg/ml
, 25th-75th percentile 1,075- 17,047; P < 0.05 compared with T-1) but faile
d to induce proinflammatory cytokines (T-2: TNF-alpha: median 0 pg/ml, 25th
-75th percentile 0-6; IL-1 beta: median 1 pg/ml, 25th-75th percentile 0-81;
nonsignificant). Removal of plasma at T-2 increased TNF-alpha response to
lipopolysaccharide (+83.8%; P < 0.05), whereas it suppressed IL-10 (-36.8%;
P < 0.05). Similarly, incubation of PBMCs (T-1) with plasma obtained after
CPB (T-2) as web as addition of IL-10 or norepinephrine in concentrations
present in plasma after CPB led to a reduced lipopolysaccharide-stimulated
TNF-alpha and an increased IL-10 response. Coadministration of norepinephri
ne and IL-10 had synergistic effects. Although pretreatment with an anti-IL
-10 antibody and labetalol before addition of plasma obtained at T-2 largel
y restored the TNF-alpha response in vitro, their addition post-treatment f
ailed to restore the monocytic TNF-alpha response.
Conclusions: Plasma contains interacting factors that inhibit the release o
f TNF-alpha and increase the release of IL-10, presumably attenuating the i
nflammatory response to CPB, Although norepinephrine fails to induce a cyto
kine response in the absence of other stimuli, its administration seems to
augment the antiinflammatory IL-10 response while attenuating the TNF-alpha
response.