Interleukin-6 (IL-6) is a multifunctional cytokine produced by macrophages, T cells, B cells, endothelial cells and tumour cells. Interleukin-6 is able to promote tumour growth by upregulating anti-apoptotic and angiogenic proteins in tumour cells. In murine models it has been demonstrated that antibodies against IL-6 diminish tumour growth. Several reports have highlighted the prognostic importance of IL-6 in e.g., prostate and colon cancer. We addressed prospectively the prognostic significance of serum IL-6 (sIL-6), measured at diagnosis of metastasis, in 96 unselected and consecutive patients with progressive metastatic breast cancer before the initiation of systemic therapy. The median sIL-6 value for the breast cancer population was 6.6 +/- 2.1 pg/ml. Patients with 2 or more metastatic sites had higher sIL-6 values compared to those with only 1 metastatic site (respectively 8.15 +/- 1.7 pg/ml and 3.06 +/- 6.6 pg/ml; p < 0.001). Patients with liver metastasis (8.3 +/- 2.4 pg/ml), with pleural effusions (10.65 +/- 9.9 pg/ml) and with dominant visceral disease (8.15 +/- 3.3 pg/ml) had significantly higher values compared to those without liver metastases (4.5 +/- 3.4 pg/ml; p = 0.001), without pleural effusions (5.45 +/- 1.5 pg/ml; p = 0.0077) and with dominant bone disease (4.5 +/- 1.4 pg/ml; p = 0.007) respectively. No correlation between sIL-6 and age, menopausal status, performance status, tumour grade, body-mass index, histology and hormone receptor status was found. Multivariate analysis showed that high levels of serum IL-6 have independent prognostic value. We conclude that circulating IL-6 is associated with worse survival in patients with metastatic breast cancer and is correlated with the extent of disease. Copyright 2002 Wiley-Liss, Inc.
