fibrin and Toxemia

The role of interleukin 6 (IL-6) in the toxic sequelae of sepsis is controversial. To assess the part of IL-6 in inflammatory responses to endotoxin, we investigated eight chimpanzees after either a bolus intravenous injection of Escherichia coli endotoxin (n = 4; 4 ng/kg) or after the same dose of endotoxin with a simultaneous bolus intravenous injection of an anti-IL-6 mAb (30 mg; n = 4). Anti-IL-6 did not affect the induction of the cytokine network (tumor necrosis factor [TNF], soluble TNF receptors types I and II, and IL-8) by endotoxin, nor did it influence the occurrence of a neutrophilic leukocytosis and neutrophil degranulation, as monitored by the measurement of elastase-alpha 1-antitrypsin complexes. In contrast, anti-IL-6 markedly attenuated endotoxin-induced activation of coagulation, monitored with the plasma levels of the prothrombin fragment F1+2 and thrombin-antithrombin III complexes, whereas activation of fibrinolysis, determined with the plasma concentrations of plasmin-alpha 2-antiplasmin complexes, remained unaltered. We conclude that IL-6 does not have a feedback effect on the release of other cytokines after injection of endotoxin, and that it is not involved in endotoxin-induced neutrophilia or neutrophil degranulation. IL-6 is, however, an important intermediate factor in activation of coagulation in low grade endotoxemia in chimpanzees.

Topics: Animals; Antibodies, Monoclonal; Blood Coagulation; Cell Count; Endotoxins; Fibrin; Humans; Injections, Intravenous; Interleukin-6; Interleukin-8; Monocytes; Neutrophils; Pan troglodytes; Receptors, Tumor Necrosis Factor; Toxemia; Tumor Necrosis Factor-alpha

Rats were inoculated with viable Salmonella dublin organisms, or a crude S dublin endotoxin, at the fourteenth and nineteenth days of pregnancy. They were killed at intervals up to 96 hours after inoculation, and the pathogenesis of the lesions was compared. At each stage of pregnancy the initial lesions produced by live bacteria and crude endotoxin showed important similarities, confirming the significance of endotoxin in the pathogenesis of placental damage. There were differences in the later stages of the pathogenic process. Comparisons of the process of placental damage at the two stages of pregnancy have suggested that the same mechanism acts throughout the last third of pregnancy and that thrombosis and disseminated intravascular coagulation are not an important part of the mechanism of placental damage.

Topics: Animals; Disseminated Intravascular Coagulation; Endotoxins; Female; Fetal Death; Fibrin; Granulation Tissue; Hemorrhage; Necrosis; Neutrophils; Placenta; Placenta Diseases; Pregnancy; Pregnancy Complications, Infectious; Rats; Salmonella Infections, Animal; Sodium Chloride; Thrombosis; Time Factors; Toxemia; Uterus

Topics: Angiography; Animals; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Embolism, Fat; Escherichia coli Infections; Female; Fibrin; Infarction; Kidney; Kidney Cortex Necrosis; Kidney Diseases; Kidney Glomerulus; Lipids; Rabbits; Shwartzman Phenomenon; Toxemia; Triglycerides

Topics: Adolescent; Adult; Cadaver; Female; Fibrin; Humans; Immunosuppressive Agents; Kidney; Kidney Glomerulus; Kidney Transplantation; Male; Renal Dialysis; Sepsis; Shwartzman Phenomenon; Toxemia; Transplantation Immunology; Transplantation, Homologous

Topics: Blood; Blood Pressure; Female; Fibrin; Humans; Hypertension; Pre-Eclampsia; Pregnancy; Serum; Thrombolytic Therapy; Toxemia