The role of pro-inflammatory cytokines and immune cells in colorectal carcinoma progression

Cytokines exhibit a pleiotropic effect in the regulation of the immune cell function, tumor growth and antitumor immune responses. A total of 30 patients with colorectal carcinoma were enrolled on this study and their levels of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, serum granulocyte colony-stimulating factor (sG-CSF) and serum macrophage colony-stimulating factor (sM-CSF) were measured preoperatively using ELISA. Tumor-infiltrating granulocyte (TIG), tumor-associated macrophage (TAM), G-CSF and M-CSF expression in tumor cells were examined using immunostaining. This study revealed abnormal levels of cytokines in patients, including IL-1β (1/30, 3.3%), IL-6 (16/30 53.3%), IL-81 (15/30, 50%), TNF-α (4/21, 19%), sG-CSF (17/30, 56.7%) and sM-CSF (4/21, 19%). There was a positive linear correlation between IL-6 and sM-CSF (P=0.017, R=0.517). sG-CSF was significantly associated with a deeper tumor invasion (P=0.039) and a more advanced tumor stage (P=0.023). The granulocyte/lymphocyte (G/L) ratio was associated with abnormal levels of sG-CSF. Logistic univariate analysis revealed that TIGs were a risk factor for lymph node metastasis (0.019) and TAMs were a risk factor for depth of invasion (0.029), but this was not confirmed in logistic multivariate analysis. In conclusion, IL-6, IL-8, sM-CSF and sG-CSF may indirectly promote tumor growth, progression and metastasis by changing the leukocyte populations in the blood and the tumor microenvironment.