WHOLE-BODY ENERGY-EXPENDITURE PROTEIN BREAKDOWN AND POLYAMINE EXCRETION DURING HIGH-DOSE TREATMENT WITH INTERLEUKIN-2 AND INTERFERON-ALPHA

Objective: To correlate changes in whole body resting energy expenditu re and protein breakdown with the production of stress hormones, excre tion of polyamines, and circulating concentrations of interleukin-1 (I L-1), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alph a), in patients undergoing treatment with high doses of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha).Design: Prospective open study . Setting: University Department of Surgery. Subjects: 11 Patients wit h malignant melanoma (n = 8) or renal cell carcinoma (n = 3) all of wh om had a Karnofsky score of 80 or more. Interventions: Daily intraveno us 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. Main outcome measures: Energy expenditure measured by indirect calorimetry, body temperature, heart rate, urina ry excretion of amino acids and nitrogen, and plasma cytokine concentr ations. Results: Three patients had a partial response. IL-1 was not d etectable in plasma; and concentrations of IL-2 increased rapidly duri ng the infusion before falling rapidly when it stopped, of IL-6 increa sed significantly (mean (SEM) 3.44 (1.6) to 11 (2) U/ml, p < 0.05), an d of TNF-alpha increased by 295% (p < 0.05). Resting energy expenditur e increased from 92 (4) to 113 (4) kJ/kg/day (p < 0.001) during the in fusion and this was accompanied by a rise in temperature and an increa se in the urinary excretion of cortisol (which also correlated with in creased breakdown of whole body protein). Conclusion: The increased en ergy expenditure and protein breakdown were probably a result of stimu lation of production of catecholamines and cortisol, as after injury, but the direct effects on temperature regulating neurons may be import ant.