Functional roles of cytokines in infectious disease associated colorectal carcinogenesis.

Infection processes induce various soluble factors that are carcinogens in humans; therefore, research into the soluble factors of chronic disease released from cells that have been infected with parasites is warranted. Parasitic infections in host cells release high levels of IFNγ. Studies have hypothesised that parasitosis-associated carcinogenesis might be analogous to colorectal cancers developed from inflammatory bowel diseases, whereby various cytokines and chemokines are secreted during chronic inflammation. IL-18 and IL-21 are other factors that might be involved in the development of colorectal cancer in schistosomiasis patients and patients with other infections. IL-21 has profound effects on tumour growth and immunosurveillance of colitis-associated tumourigenesis, thereby emphasising its involvement in the pathogenesis of colorectal cancer. The prominent role of IL-21 in antitumour effects greatly depends on the enhanced cytolytic activity of NK cells and the pathogenic role of IL-21, which is often associated with enhanced risks of cancer and chronic inflammatory processes. As IL-15 is also related to chronic disease, it is believed to also play a role in the antitumour effect of colorectal carcinogenesis. IL-15 generates and maintains long-term CD8+ T cell immunity against T. gondii to control the infection of intracellular pathogens. The lack of IL-15 in mice contributes to the downregulation of the IFNγ-producing CD4+ T cell response against acute T. gondii infection. IL-15 induces hyperplasia and supports the progressive growth of colon cancer via multiple functions. The limited role of IL-15 in the development of NK and CD8+ T cells suggests that there may be other cytokines compensating for the loss of the IL-15 gene.