Rhesus differential susceptibility to endotoxin is not associated with activation of plasma prekallikrein.
This study is part of a project aimed at understanding individual responses to acute endotoxemia in a catheter-free rhesus (Macaca mulatta) model of inflammation. In the previous study [J. Endotoxin Res. 2 (1995) 411-420.], we showed that of 14 endotoxin 0111:B4 (ETX)-infused monkeys, only three died at < 13.5 h and one at 6 days postinfusion. Doses of ETX correlated neither with the magnitude of hypotension nor with rhesus outcome. Survival (and death at 6 days) or death at < 13.5 h was rather associated with controllable or uncontrollable rise of plasma levels of proinflammatory cytokines and reversible or irreversible shock. In the current study, we used plasmas of 5 survivors and of one of the monkeys that died at < 13.5 h (each infused with 3 X 10(6) EU ETX/kg), and of two saline control monkeys of the previous study. We analyzed changes in parameters of coagulation and contact systems. After ETX infusion, activated partial thromboplastin time (APTT) and prothrombin time (PT) values increased modestly in survivors but markedly in the nonsurvivor; responses of platelet counts and levels of fibrinogen, antithrombin, alpha2-macroglobulin (alpha2M), Cl-inhibitor (C1INH) and alpha1 -antitrypsin were similar in survivors and the nonsurvivor; the rate of plasma prekallikrein (PK) activation measured by hydrolysis of the kallikrein (KAL) substrate D-Pro-Phe-Arg-p-nitroanilide was not altered by ETX infusion; and the distribution of PK activation products, analyzed by MAb 13G11/immunoblotting in plasmas with or without artificial activation, was similar in survivors and the nonsurvivor. Responses in controls were relatively stable. Since we used defined experimental conditions, this primate model has the potential to be useful to study further correlation of inflammatory parameters with differential outcome.
Veloso
D
D
Division of Medicine, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA. dveloso@msi.uth.tmc.edu
Smith
J I
JI
Cosgriff
T M
TM
D000818:Animals; D004731:Endotoxins / Q000633:toxicity*; D007249:Inflammation / Q000097:blood*; D008253:Macaca mulatta; D010314:Partial Thromboplastin Time; D011288:Prekallikrein / Q000378:metabolism*; D011517:Prothrombin Time; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D011288:Prekallikrein