It has been suggested that, as part of the inflammatory response to the presence of a tumor, various cytokines are produced and these induce hepatic synthesis of acute-phase proteins (APP). Under these circumstances it is not known what changes occur in the fixed component of hepatic protein synthesis. The aim of this study was to compare circulating interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) concentrations and fixed hepatic protein synthesis rates in a group of healthy controls (n = 6) with a group of patients with an established APP response secondary to hepatic metastasis from colorectal cancer (n = 6). Fixed hepatic protein synthesis rates were measured following a primed, constant 20-hour infusion of 15N-glycine. The liver was biopsied at laparotomy. The APP response was assessed by serum C-reactive protein concentration and cytokines were assayed by a combination of immunoassay and bioassay. The patients with advanced cancer and an on-going APP response had elevated circulating IL-6 concentrations (p less than 0.01). Rates of fixed hepatic protein synthesis were 30% lower than those observed in controls (p less than 0.01). These findings demonstrate that in patients with hepatic metastasis, although the synthesis of certain acute-phase export proteins can be increased, fixed protein synthesis is reduced. Whether these changes in the distribution of hepatic protein synthesis are mediated by IL-6 will require further investigation.
The aim of this study was to determine whether administration of the non-steroidal anti-inflammatory agent ibuprofen might attenuate the acute-phase response in patients with colonic cancer. Cytokines and acute-phase proteins were measured before administration of ibuprofen and again 3 days later, when protein synthesis was measured using 15N-glycine. In patients with cancer, ibuprofen caused a significant reduction in the plasma concentration of all five acute-phase proteins studied. Although interleukin 6 levels were raised, they did not change following administration of ibuprofen. Unlike the situation in patients with cancer who did not receive ibuprofen, whole-body protein kinetics were similar to those of control subjects in patients with cancer who received ibuprofen. Whether or not ibuprofen had been administered, non-export hepatic protein synthesis rates were significantly lower in patients with than in those without cancer. These results suggest that short-term administration of ibuprofen can attenuate accelerated whole-body protein kinetics and the acute-phase response in patients with advanced cancer.
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