Recent investigations suggest that proinflammatory
cytokines such as
IL-6 and
IL-8 are involved in the development of
colorectal cancer (CRC), whereas
statins, primarily used to decrease high levels of blood
cholesterol, exhibit pleiotropic effects on
carcinogenesis. In the present study we compared the expression of
IL-8 and
IL-6 in tissue samples of
tumor and adjacent normal colon mucosa obtained from patients with advanced
colorectal cancer (CRC). The analysis of mRNAs expression for these proinflammatory
cytokines determined by RT-PCR showed a higher level of IL-8-mRNA in
tumor tissue than in normal mucosa, while
IL-6 was similarly expressed in
tumor and normal tissue. The mean values of serum levels of both
IL-6 and
IL-8 were significantly higher in CRC patients than in healthy volunteers. Surgical removal of the
tumor resulted in a prompt decrease of serum level of
IL-8 already on the third day, whereas
IL-6 level was transiently increased to become lower only after 7-10 days. Treatment of CRC with
simvastatin (80 mg/day for 14 days) led to a significant decrease of serum
IL-6, while the
IL-8 level was less affected. The in vitro experiments on
colorectal cancer-derived cell lines (HT-29 and Caco-2) demonstrated that application of
simvastatin decreased generation of both
IL-6 and
IL-8. The differences in response of serum levels of
IL-6 and
IL-8 after
tumor removal and treatment with
simvastatin are novel observations suggesting distinct pathological roles of the two
cytokines in CRC development. We conclude that 1) colorectal
carcinogenesis is accompanied by increased synthesis and release of proinflammatory
cytokines such as IL-6 and IL-8; 2)
simvastatin therapy results in a decrease in serum level of proinflammatory
cytokines, especially IL-6 in CRC and 3)
simvastatin inhibits release of IL-8 and IL-6 from colorectal cell lines.