Does heart surgery change the capacity of α1-antitrypsin to inhibit the ATP-induced release of monocytic interleukin-1β? A preliminary study.

Heart surgery involving cardiopulmonary bypass induces systemic inflammation that is, at least in part, caused by extracellular ATP originating from damaged cells and by proteases secreted by activated neutrophils. The anti-protease α1-antitrypsin (AAT) forms complexes with several proteases including neutrophil elastase, resulting in a mutual loss of activity. We demonstrated recently that AAT inhibits the ATP-induced release of the pro-inflammatory cytokine interleukin-1β by human monocytes by a mechanism involving activation of metabotropic functions at nicotinic acetylcholine receptors. Interleukin-1β importantly contributes to the pathogenesis of sterile inflammatory response syndrome. Thus, AAT might function as an endogenous safeguard against life-threatening systemic inflammation. In this preliminary study, we test the hypothesis that during cardiopulmonary bypass, AAT is inactivated as an anti- protease and as an inhibitor of ATP-induced interleukin-1β release. AAT was affinity-purified from the blood plasma of patients before, during and after surgery. Lipopolysaccharide-primed human monocytic U937 cells were stimulated with ATP in the presence or absence of patient AAT to test for its inhibitory effect on interleukin-1β release. Anti-protease activity was investigated via complex formation with neutrophil elastase. The capacity of patient AAT to inhibit the ATP-induced release of interleukin-1β might be slightly reduced in response to heart surgery and complex formation of patient AAT with neutrophil elastase was unimpaired. We conclude that surgery involving cardiopulmonary bypass does not markedly reduce the anti-inflammatory and the anti-protease activity of AAT. The question if AAT augmentation therapy during heart surgery is suited to attenuate postoperative inflammation warrants further studies in vivo.