TNF and irritable bowel syndrome: CRP is a true acute-phase protein produced in hepatocytes in response to tumor necrosis factor, interleukin-1, and interleukin-6,26 whereas calprotectin is mainly an intracellular protein in the cytosol of neutrophils, and elevated calprotectin levels mirrors increased neutrophil activity.13,14 Perhaps, the neutrophil activity, especially in blood, or the transmission of calprotectin from the gut to blood, or both, is a later event in the evolution of IBD.