Does interleukin-6 link explain the link between tumour necrosis, local and systemic inflammatory responses and outcome in patients with colorectal cancer?

Cancer-associated inflammation has been identified as a key determinant of disease progression and survival in colorectal cancer. In particular, it has been consistently reported that both the local and systemic inflammatory responses play an important role in determining outcome in colorectal cancer. Given the importance of cancer-associated inflammation, up-regulation or attenuation of these respective inflammatory responses may be important for progression and survival in colorectal cancer. Recent work has focused on the inter-relationships between the tumour and these key inflammatory processes. In particular, tumour necrosis has been reported to be associated with decreased local inflammatory infiltrate and with elevated markers of systemic inflammation in colorectal cancer and has been proposed as a potential link between the systemic and local inflammatory responses. Thus there is increasing interest in the potential biochemical mediators of this link. In this review we examine the evidence for IL-6 in the natural history of colorectal cancer and its relationship with tumour necrosis and the local and systemic inflammatory responses. There is now good evidence that tumour concentrations of IL-6 have been directly associated with increased necrosis, proliferation, differentiation and vascular invasion, while circulating concentrations of IL-6 are directly associated with T-stage, CRP concentrations and poorer survival. Also, interleukin-6 and down-stream pathways, such as the JAK/STAT pathway, have emerged as important factors in the modulation of cancer-associated inflammation. Therefore, IL-6 has emerged as a key mediator of the relationship between tumour necrosis, local and systemic inflammatory responses and outcome in patients with colorectal cancer.