Cytokines, the acute-phase response, and resting energy expenditure in cachectic patients with pancreatic cancer.

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 that in those without (TNF: 1231 +/- 244 vs. 210 +/- 54 pg/ml/10(5) cells; p < 0.001; IL-6: 11.5 +/- 1.7 vs. 3.6 +/- 1.4 ng/mL/10(5) 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 of 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.

• Authors: J S Falconer, K C Fearon, C E Plester, J A Ross, D C Carter
• Journal: Annals of surgery (Ann Surg) Vol. 219 Issue 4 Pg. 325-31 (Apr 1994) ISSN: 0003-4932 [Print] United States
• PMID: 7512810 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acute-Phase Proteins
• Cytokines
• Interleukin-6
• Tumor Necrosis Factor-alpha

Topics

• Acute-Phase Proteins (metabolism)
• Acute-Phase Reaction (blood, physiopathology)
• Basal Metabolism
• Cachexia (blood, physiopathology)
• Cytokines (blood, physiology)
• Female
• Humans
• Interleukin-6 (blood)
• Male
• Middle Aged
• Pancreatic Neoplasms (blood, physiopathology)
• Tumor Necrosis Factor-alpha (metabolism)