Elevated proinflammatory cytokine IL-17A in the adjacent tissues along the adenoma-carcinoma sequence.

Considerable evidence has suggested that chronic inflammation is a causative factor in the development of human colorectal cancer (CRC). Interleukin (IL)-17A produced mainly by Th17 cells is a novel proinflammatory cytokine and increased IL-17A is associated with colorectal neoplastic transformation. In this study, we have evaluated the expression of IL-17A in the adjacent tissues along the colorectal adenoma-carcinoma sequence. The expression of IL-17A in the adjacent tissues of colorectal adenoma (adenoma-adjacent, n = 32) and sporadic CRC (CRC-adjacent, n = 45) was examined. In addition, the expression pattern of Th17 cell differentiation stimulators (IL-1β, IL-6 and IL-23A) in the adjacent tissues were also examined. The results showed that the expression level of IL-17A mRNA was non-statistically increased (4-fold higher) in the adenoma-adjacent tissues and it became significantly increased (9-fold higher) in the CRC-adjacent tissues as compared with the control. The expression level of IL-17A in the CRC-adjacent tissues was not associated with CRC clinicopathological parameters and overall survival. Immunohistochemistry confirmed an increased density of intraepithelial IL-17A expressing cells in the CRC-adjacent tissues. The Th17 cell differentiation simulators IL-1β and IL-6 were also shown in an increase trend from the adenoma-adjacent to CRC-adjacent tissues. These results provide evidence that IL-17A/Th17 response is enhanced in the adjacent tissues during the colorectal neoplastic transformation.