Oxidative autoaggression by phagocytes in human peritonitis

In 60 abdominal exudates from patients with the diagnosis of either acute or persistent (chronic) peritonitis, indicators of phagocyte-derived oxidative systems (myeloperoxidase, chemiluminescence) and proteases (elastase) were measured. These exudates reveal a picture of maximal inflammatory activation. Both types of exudates (30 each) showed a significant influx of inflammatory cells, with the mean leucocyte count being 73000 μL and 32000 μL -1 ' respectively. Local myeloperoxidase concentrations were approximately 1000-fold greater than that of normal plasma. Spontaneous and elicitable chemiluminescence-indicators of phagocyte respiratory burst activity-were dramatically increased. In addition, levels of extracellularly released elastase (from neutrophils) were found to be up to about 1000-fold that of normal plasma values. Although most of the elastase detected in the exudates was complexed with α 1 -proteinase inhibitor (α 1 PI), enzymatically active elastase could be measured in approximately 60% of the samples being investigated. As there was an excess of immunoreactive α 1 PI in these exudates, the free elastase activity implies that much of the α 1 PI was inactive, presumably subjected to oxidative destruction. Moreover, a trypsin-inhibitory activity to antigen ratio below I (mean =0.81) in 75% of the purulent exudates indicated also partial proteolytic degradation of α 1 PI. In contrast, 16 clear exudates (no bacteria, white cell count below 500 μL -1 ) taken from the non-infected peritoneal cavity of patients undergoing intra-abdominal surgery revealed a similar permeability increase of the peritoneum but did not show relevant oxidative and proteolytic activity or destruction of α 1 PI compared with purulent specimens. Thus, only the inflammatory process of peritonitis appears to result in an overwhelming local phagocytic activity that initiates and maintains protease inhibitor consumption and/or inactivation. The tremendous oxidative potential found in purulent exudates may cause destruction in a wide variety of defence systems.