INTERACTION OF BORRELIA SPIROCHETES WITH HUMAN MONONUCLEAR LEUKOCYTES CAUSES PRODUCTION OF LEUKOCYTIC PYROGEN AND THROMBOPLASTIN

Abstract

Relapsing fever caused by Borrelia spirochetes is characterized by episodes of spirochetemia, fever and DIC (disseminated intravascular coagulation). The ability of B. hermsii to induce production of leukocytic pyrogen and thromboplastin from human blood leukocytes in vitro was investigated. Organisms were found devoid of endotoxin by the Limulus assay. Human peripheral blood leukocytes were separated into MNC [mononuclear cell] and PMN [polymorphonuclear cell] fractions and were incubated with 2-5 spirochetes per cell in 10% human serum. Supernatant fluids from MNC-spirochete mixtures produced mean increases in the temperature of rabbits of 0.80.degree.-1.35.degree. C, which were significantly higher than those caused by supernatant fluids of MNC or spirochetes alone (P < 0.05). MNC-spirochete mixtures possessed 7-15 times the thromboplastic activity of MNC suspensions alone, assayed with a modified 1-stage prothrombin time. Supernatant fluids of PMN and spirochetes did not contain leukocytic pyrogen and PMN suspensions did not produce thromboplastin. Cycloheximide (10 .mu.g/ml), an inhibitor of protein synthesis, completely suppressed both pyrogen and thromboplastin production. Although intracellular spirochetes were observed within phagosomes of blood monocytes by EM, the production of leukocytic pyrogen and thromboplastin was not significantly altered by serum opsonins or by the inhibitors of phagocytosis cytochalasin B (5 .mu.g/ml) or phenylbutazone (2 mg/ml). Borrelia spirochetes apparently stimulated human MNC to produce increased amounts of leukocytic pyrogen and thromboplastin. This stimulation required de novo synthesis of protein, was not mediated by endotoxin and was not prevented by omitting opsonic proteins or by inhibiting phagocytosis.