Tumour necrosis factor-mediated release of plasminogen activator inhibitor 1 by human peritoneal mesothelial cells

Human mesothelial cells synthesize plasminogen activator inhibitor (PAI) 1 in inflamed peritoneal tissue. The role of tumour necrosis factor (TNF) in the mediation of this response was studied. Postoperative peritoneal drain fluid contained both TNF and PAI-1. Peak levels of TNF at 4 h (median 271 pg/ml) preceded a rise in PAI-1 concentration, which peaked at 18 h (median 943.1 ng/ml). Thus TNF may mediate increased PAI-1 release in inflamed peritoneum. TNF significantly increased the mean(s.e.m.) release of PAI-1 by human peritoneal mesothelial cells in vitro at 4 h (control 1.84(0.17) ng/micrograms versus TNF 2.37(0.17) ng/micrograms, P < 0.05), 6 h (2.53(0.09) versus 3.88(0.46) ng/micrograms, P < 0.05), 18 h (0.50(0.02) versus 1.04(0.11) ng/micrograms, P < 0.05) and 24 h (0.87(0.05) versus 1.35(0.11) ng/micrograms, P < 0.05). TNF may be an important mediator of PAI-1 production by human mesothelial cells during peritoneal inflammation.