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We have previously suggested that colorectal liver metastases might produce 'toxins' that reduce both quality of life (QoL) and survival. In this study we assessed whether QoL in patients with such metastases was related to immune activation, as determined by increased serum levels of interleukin 6 (IL6), soluble tumour necrosis factor receptor 1 (sTNFr1), soluble interleukin 2 receptor alpha (sIL2rα) or the interferon-γ marker neopterin.Serum IL6, sTNFr1, sIL2rα, neopterin, alkaline phosphatase and carcinoembryonic antigen levels, liver metastasis volume, and QoL (Hospital Anxiety and Depression [HAD] scale, Rotterdam Symptom Checklist [RSC], and Sickness Impact Profile [SIP]) were measured in 43 patients. There were significant positive correlations between serum sIL2rα and HAD depression score (r=0.66, P=0.0001), RSC physical symptom score (r=0.46, P<0.01), and SIP score (r=0.47, P=0.009). Multiple regression analysis suggested that serum sIL2rα level was a significant independent predictor of HAD depression score. Although survival was shorter (logrank test P<0.05) where sIL2rα, sTNFr1 and IL6 levels were higher, the ability of sIL2rα to predict HAD depression score was independent of survival.