However, the fibrinolytic activity was rapidly offset by the subsequent and long-lasting increase in the plasma levels of PAI-1.11,33 A marked increase in plasma PAI-1 during endotoxemia has consistently been found in every animal species.33,103 Studies at tissue level in animals challenged with endotoxin or TNF showed a strong elevation of PAI-1 mRNA in tissues, including those most commonly affected by microthrombi during sepsis (kidney, adrenals, lung and liver). This evidence concerns the gene TNF and serum lipopolysaccharide activity.