Whole body energy expenditure protein breakdown and polyamine excretion during high dose treatment with interleukin-2...

To correlate changes in whole body resting energy expenditure and protein breakdown with the production of stress hormones, excretion of polyamines, and circulating concentrations of interleukin-1 (IL-1), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha), in patients undergoing treatment with high doses of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha).

Prospective open study.

University Department of Surgery.

11 Patients with malignant melanoma (n = 8) or renal cell carcinoma (n = 3) all of whom had a Karnofsky score of 80 or more.

Daily intravenous infusion of IL-2 (18 x 10(6) IU/m2/day) and subcutaneous injection of IFN-alpha (3 x 10(6) IU/m2/day) for days 1-5 and 8-12 in two courses with a three week interval.

Energy expenditure measured by indirect calorimetry, body temperature, heart rate, urinary excretion of amino acids and nitrogen, and plasma cytokine concentrations.

Three patients had a partial response. IL-1 was not detectable in plasma; and concentrations of IL-2 increased rapidly during the infusion before falling rapidly when it stopped, of IL-6 increased significantly (mean (SEM) 3.44 (1.6) to 11 (2) U/ml, p < 0.05), and of TNF-alpha increased by 295% (p < 0.05). Resting energy expenditure increased from 92 (4) to 113 (4) kJ/kg/day (p < 0.001) during the infusion and this was accompanied by a rise in temperature and an increase in the urinary excretion of cortisol (which also correlated with increased breakdown of whole body protein).

The increased energy expenditure and protein breakdown were probably a result of stimulation of production of catecholamines and cortisol, as after injury, but the direct effects on temperature regulating neurons may be important.