Plasma Cytokines as Potential Response Indicators to Dietary Freeze-Dried Black Raspberries in Colorectal Cancer Patients

Oral consumption of freeze-dried black raspberries attenuated neoplastic changes in colorectal tissue markers of apoptosis, cell proliferation, and angiogenesis in colorectal cancer (CRC) patients. To determine whether plasma concentrations of interleukin (IL)-1 beta, IL-2, IL-6, IL-8, IL-10, IL-12p70, granulocyte macrophage colony stimulating factor (GM-CSF), interferon-gamma, and tumor necrosis factor-alpha (TNF-alpha) were associated with berry treatment and changes in colorectal tissue markers of apoptosis, cell proliferation, and angiogenesis, plasma and biopsy samples of adenocarcinoma and adjacent normal-appearing colorectal tissue were collected before and during berry treatment from 24 CRC patients who had not received prior therapy and drank a slurry of black raspberry powder (20 g in 100 ml drinking water) 3 times a day for 1 to 9 wk. Plasma concentrations of GM-CSF (+0.12 +/- 0.04 pg/mL; P = 0.01) and IL-8 (-1.61 +/- 0.71 pg/mL; P = 0.04) changed in patients receiving berries for more than 10 days. These changes were correlated with beneficial changes in markers of proliferation (r(Delta GM-CSF), (Delta Ki67 carcinoma -) (normal) = -0.51) and apoptosis (r(Delta IL-8, Delta TUNEL carcinoma - normal) = -0.52) observed in colorectal tissue taken within the same week. Plasma concentrations of GM-CSF and IL-8 may serve as noninvasive indicators to monitor tissue response to berry-based interventions for CRC.