Aprotinin® diminishes inflammatory processes

Abstract Many of the recent reports concerning cytokine levels in cardiopulmonary bypass have documented changes in the levels of these trauma indicators. In the present report, we also document their levels but in the presence of Aprotinin R . Aprotinin R is a protease inhibitor used not only to diminish bleeding, but also to diminish elements of the diffuse inflamatory response associated with this type of surgery. We report in plasma obtained from 20 patients that initially interleukin-8 (IL-8) levels (53.4 ± 7 pg/ml plasma to 185.5 ± 30 pg/ml) increased 20 min from the start of surgery. This is followed by IL-6 (5.3 ± 1.1 to 200 ± 50 pg/ml) peaking 15 h post surgery. These levels return to normal by day 3 postop. IL-1β and tumour necrosis factor (TNF) levels remained at baseline for the observation period. Associated with these changes in cytokine levels is the activity state of immunocytes (granulocytes and monocytes) noted by conformational changes obtained from computer-assisted microscopy. The cells exhibited an ameboid conformation and became mobile (67%), peaking at 120 min after surgery began and returned to a more rounded conformation with only 6% exhibiting the ameboid conformation by day three. In in-vitro experiments, where immunocytes not exposed to cardiopulmonary bypass were exposed to plasma obtained from patients having undergone this surgery, their activity level rose to 65%. In the same experiment, when Aprotinin ® was added to the cell-plasma mixture, the level of activation dramatically dropped to 25%. Thus, aprotinin ® was found at high doses to lower cytokine and cellular activation associated with the acute inflammatory responses of cardiopulmonary bypass, suggesting that this may be initiated by hyperstimulated immunocytes.