Cytokines, the Acute-Phase Response, and Resting Energy Expenditure in Cachectic Patients with Pancreatic Cancer

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Abstract

Objective

To determine whether resting energy expenditure (REE) is increased in cachectic patients with pancreatic cancer and to define the relation of tumor necrosis factor (TNF) and interleukin-6 (IL-6) production to the acute-phase response and to REE.

Methods

Measurement of REE (indirect calorimetry) and assessment of body composition (bioelectrical impedance analysis) were done in 21 patients with unresectable pancreatic cancer and on 16 age-related controls. The systemic inflammatory response in peripheral blood of the cancer patients was assessed using the acute-phase protein, C-reactive protein, and the cytokines TNF and IL-6. Production of these cytokines by peripheral blood mononuclear cells in vitro was also measured.

Results

Patients with pancreatic cancer had an elevated REE when compared with controls (73.4 ± 5.0 vs. 53.5 ± 1.6 kcal/kg body cell mass; p < 0.003). Resting energy expenditure was significantly greater in cancer patients with an acute-phase response (C-reactive protein > 10 mg/L) than in those who did not have such a response (85.5 ± 10.0 [n = 9] vs. 64.3 ± 3.0 [n = 12] kcal/kg body cell mass; p < 0.04). Tumor necrosis factor was not detected in the serum of any of the cancer patients. Serum IL-6 was detected but levels were not significantly different among cancer patients with or without an acute-phase response. In contrast, spontaneous production of TNF and IL-6 by isolated peripheral blood mononuclear cells was significantly greater in cancer patients with an acute-phase response than in those without (TNF: 1231 ± 244 vs. 210 ± 54 pg/mL/105 cells; p < 0.001; IL-6: 11.5 ± 1.7 vs. 3.6 ± 1.4 ng/mL/105 cells; p < 0.003).

Conclusions

In pancreatic cancer at least a component of weight loss is due to increased REE. Furthermore, the presence of an acute-phase response identifies a group of patients who are markedly hypermetabolic. The serum concentration of TNF or IL-6 does not correlate with the presence of an acute-phase response, whereas rates of cytokine production by peripheral blood mononuclear cells are significantly greater in patients with such a response. This suggests that local rather than systemic cytokine production may be important in regulating the acute-phase response.

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