CYTOKINE-INDUCED RELEASE OF PLASMINOGEN-ACTIVATOR INHIBITOR-1 BY HUMAN MESOTHELIAL CELLS

Objective: To see what effect the inflammatory cytokines tumour necros is factor (TNF), interleukin 1 (IL-1), and interleukin 6 (IL-6) had, b oth alone and in combination, on the production of plasminogen activat or inhibitor 1 (PAI-1) by human mesothelial cells. Design: Laboratory study. Setting: University hospital, UK. Material: Six cell cultures o f human mesothelial cells. Main outcome measures: Concentrations of PA I-1 in conditioned media and cell lysates after culture for 24 hours. Results: TNF IL-1, and IL-6 all significantly increased the amount of PAI-1 in the media compared with controls (81%, p < 0.05; 77%, p < 0.0 5; and 60%, p < 0.05, respectively). TNF and IL-1 together produced si gnificantly more release than each cytokine alone (190%, P < 0.05) and a combination of the three increased release even further (290%, p < 0.05). The presence of endotoxin did not significantly affect the rele ase of PAI-1. Conclusion: Inflammatory cytokines mediate the release o f PAI-1 by mesothelial cells, and so may affect the deposition of fibr in within the peritoneal cavity.