Pathophysiology of Relapsing Fever: Interaction of Borrelia Spirochetes with Blood Mononuclear Leukocytes Causes Production of Leukocytic Pyrogen and Tissue Thromboplastin

摘要

Relapsing fever caused by Borrelia spirochetes is characterized by episodes of spirochetemia, fever, and disseminated intravascular coagulation (DIC). We examined the ability of Borrelia hermsii, which does not contain endotoxin, to induce production of leukocytic pyrogen and thromboplastin from human blood leukocytes in vitro. Cultures of B. hermsii were washed with pyrogen-free saline. Mononuclear cells (MNC) were separated from blood by Ficoll-Hypaque gradient sedimentation and incubated with 2-5 spirochetes per MNC in 10% human serum. Supernatants from 5 times 10 to the 7th power cells were assayed in rabbits for fever production. Intact MNC were simultaneously assayed for thromboplastin activity with a modified one-stage prothrombin time employing normal human plasma and plasma deficient in individual coagulation factors. Supernatants of the MNC-spirochete mixtures produced mean increases in temperature of 0.80-1.35 deg C, which were significantly higher than supernatants of MNC, 0.13 deg C, or spirochetes alone, 0.10 deg C (p less than 0.05). MNC-spirochete mixtures possessed 7 to 15 times the thromboplastin activity of MNC suspensions. Promotion or inhibition of phagocytosis by adding respectively immune rabbit serum or cytochalasin B did not alter production of leukocytic pyrogen or thromboplastin.