Therapeutic potential for cancer cachexia by modulating the tumor-host inflammatory interactions

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Previously, we demonstrated that the tumor. host inflammatory interactions play an important role in the formation of cancer cachexia. We also showed that the top of tumor. host inflammatory interactions is the Interleukin(IL)-1-IL-6 cascade. Firstly, we evaluated the status of cancer cachexia in patients with colorectal cancer(CRC). We sought to investigate the possibility of therapeutic potential of IL-1 receptor antagonist(ra) for of patients' cachexia by modulating IL-1-IL-6 cascade. In 300 patients with CRC, there is significantly negative correlation between serum C reactive protein(CRP) and serum albmin. We divided CRC patients into four groups ; group A : CRP<0.5 mg/dl and albumin> 3.5 g/dl, group B : CRP<0.5 mg/dl and albumin<3.5 g/dl, group C : CRP> 0.5 mg/dl and albumin> 3.5 g/dl, group D : CRP> 0.5 mg/dl and albumin<3.5 g/dl. Approximately 60% of patients with stage IV CRC belong to the group C or D, indicating that these patients may have the pre-cachexic or cachexic state … More . Approximately 30% of patients with stage III CRC belong to the group C or D. Even in patients with stage I or II CRC, 15-30% of them belong to these groups. This cancer cachexia scoring system is associated with disease recurrence of CRC patients with curative surgery. With regard to the measurement of IL-1 beta and IL-6 in both cancer and adjacent normal tissue, the expression of these pro-inflammatory cytokines in patients with group D is approximately four to five times higher than those with the other groups. Experimentally, IL-1ra inhibits the expressions of soluble IL-6 and soluble glycoprotein 130 in HT29 colorectal cancer cell line. IL-1 beta enhances the expressions of soluble IL-6 and soluble glycoprotein 130. The simultaneous administration of IL-1ra and IL-1 beta slightly enhances these expressions, compared with the control. These results suggest that the cancer cachexia scoring system based on the serum CRP and albumin is associated with colorectal cancer progression and the tumor-host cytokine imbalance. The control of IL-1-IL-6 cascade may contribute the improvement of cancer cachexia and cancer progression in colorectal cancer. Less