The tissue distribution of tumor necrosis factor-alpha in rats: A compartmental model

Tumor necrosis factor (TNF) is widely accepted to be the mediator of the ca scade of metabolic abnormalities associated with both critical and chronic illness. TNF binding to cell surface receptors mediates its physiologic act ions, although the exact mechanism of TNF action is unknown. Therefore, thi s study was designed to investigate the in vivo metabolism of TNF using a m athematical model to examine tissue uptake and loss of TNF over time. Two d istinct patterns of TNF uptake were observed. Muscle tissues were found to accumulate TNF over the entire experimental period, whereas the visceral or gans were found to have a rapid initial accumulation of TNF followed by a r apid loss of TNF back to the plasma or out into the bile or the urine. Thes e patterns of TNF binding and retention may reflect the number of TNF recep tors or their affinity for TNF, as well as the balance between cell surface and soluble TNF receptors. Furthermore, TNF binding patterns provide insig ht into the biologic action of TNF at these sites. Copyright (C) 2000 by W. B. Saunders Company.