Role of lysosomes and cathepsin inhibitor in plasma during pneumococcal infection

Rabbits with lethal pneumococcal bacteremia were grouped according to progressive changes in temperature, cardiac output, blood pH, and blood lactate. Liver, heart, and skeletal muscle granular and soluble fractions were assayed for cathep- sin and beta-glucuronidase. Although various significant alterations were noted, none were consistent and none correlated well with lethality. Plasma cathepsin diminished in all groups. Plasma from rabbits with pneumococcal bacteremia and from rabbits made neutropenic with HN2 inhibited cathepsin of liver and heart. The unsedimentable fraction of liver and heart from infected animals also contained the inhibitory factor. Plasma containing the inhibitory factor did not inhibit the local Schwartzman phenomena. A similar inhibitory factor was found in plasma from patients with bacterial infections. The acid proteinase inhibitor was nondialyz- able, heat-labile, precipitated by 50% to 90% ammonium sulfate, and migrated with alpha-1 globulins. The biochemical characteristics suggest similarity to other proteinase inhibitors, but its exact role in infection has yet to be demonstrated.