Q:

Which of the following statements regarding TNFa are true?

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Which of the following statements regarding TNFa are true? 


  1. TNFa has a marked procoagulant effect
  2. Passive immunization of patients with neutralizing antibodies to TNFa improves survival from multi-organ system failure
  3. TNFa upregulates E-selectin expression
  4. The most potent known stimulus for TNFa production and release is IL-1

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a. TNFa has a marked procoagulant effect

c. TNFa upregulates E-selectin expression

TNFa has a marked procoagulant effect on endothelial cells, precipitating intravascular thrombosis. TNFa causes endothelial cells to release procoagulant activity (tissue factor), platelet activating factor, and von Willebrand factor, all of which favor thrombosis. TNFa also down regulates the expression of thrombomodulin, which has the potential to block the assembly of protein C and protein S complexes, further decreasing the anticoagulant properties of the endothelial cell surfaces. Administration of recombinant TNFa to experimental animals produces a clinical syndrome similar to that seen in septic shock and multi-organ system failure in humans. Passive immunization of animals with neutralizing antibodies against TNFa, prior to the infusion of TNFa or endotoxin, has been shown to prevent the development of this syndrome. No such evidence exists in human patients. TNFa upregulates a variety of leukocytic adhesion molecules including ICAM-1, PECAM-1, VCAM-1, E-selectin and Pselectin. A variety of exogenous and endogenous factors (including IL-1) are capable of inducing cells to produce TNFa, however the most potent stimulus for TNFa production and release is endotoxin.

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