Evolution of plasminogen activator inhibitor type 1 in patients with septic shock — correlation with cytokine concentrations

Abstract

Serum concentrations of plasminogen activator inhibitor type 1 (PAI-1), of tumor necrosis factor alpha (TNFα), interferon alpha (IFNα), interferon gamma (IFNγ), interleukin 1 β (IL-β and interleukin 6 (IL-6) were measured in 51 patients with septic shock. PAI-1 concentrations at onset of shock correlated with those of TNFα (Spearman's rank correlation coefficient: r=0.383; p=0.007) and of IL-6 (r=0.529; p=0.0002), weakly with those of IFNγ (r=0.262; p=0.06), but not with ILB and IFNα (r=0.063 and -0.081, respectively). Within one day after admission PAI-1 concentrations decreased significantly (Wilcoxon signed rank test, p<0.0001) from 360ng/ml (median, 10–90% range: 54 6000ng/ml) to 144ng/ml (45–1200). IL-6 levels also decreased significantly (<0.0001) during the first day, whereas TNFot levels did not change. Extreme PAI-1 levels (>550ng/ml) at study entry were associated with a high mortality (12 out of 16 died within a week). PAI-1 concentrations decreased in all 11 patients (and normalised in 9) that survived the first 24 h. Despite normalisation of PAI-1, 7 of these patients died within a week, whereas of the 35 patients with initial PAI-1 levels below 550 ng/ml, only 3 died within a week. In conclusion, in patients and septic shock, PAI-1 levels at study entry correlate strongly with TNFα and IL-6. At study entry extreme PAI-1 levels are associated with a poor prognosis, but normalisation of PAI-1 within a day does not improve the prognosis.