What is wrong with granulocytes in inflammatory bowel diseases?

The neutrophil plays a central role in the acute inflammatory response, a crucial mechanism required for the efficient clearance of invading microorganisms and antigenic material. Patients with primary immunodeficiencies of neutrophil function, particularly chronic granulomatous disease, are predisposed to develop bowel inflammation that is indistinguishable from Crohn's disease (CD) on the basis of clinical, endoscopic and histopathological features. The intrinsic function of the neutrophil is normal in the vast majority of patients with CD; however, there is clear evidence of an impairment of neutrophil recruitment to sites of trauma and bacterial infection. This is associated with an inability to adequately clear bacteria that have penetrated the tissues, resulting in the formation of granulomata, the histological hallmark of the disease, and the subsequent initiation of a chronic adaptive immune response. The reduced secretion of proinflammatory cytokines by macrophages, most notably TNF-α, may account for the attenuated neutrophil recruitment observed in CD. Stimulation of the innate immune system in CD, particularly in patients in remission, may be an alternative therapeutic strategy that could reduce the risk of future disease relapses.