Is Crohn’s due to sick phagocytes? ▸

Thirty years ago, Segal and Loewi suggested that acute inflammatory responses were impaired in Crohn’s disease (Lancet 1976;2:219), and it is well known that certain diseases affecting neutrophil function such as chronic granulomatous disease and glycogen storage disease 1b cause Crohn’s-like intestinal damage. Professor Segal has revisited this concept and provided more evidence of a systemic defect in acute inflammation in Crohn’s.

Using rectal or ileal biopsies taken at the site of a biopsy six hours earlier, the investigators from University College Hospital, London, showed impaired accumulation of neutrophils and reduced interleukin 8 (IL-8) production in response to gut trauma, while responses in ulcerative colitis (UC) bowel were the same as in healthy controls. They went on to demonstrate this was a generalised defect (not local to the gut) using skin windows, with impaired migration of neutrophils in Crohn’s, but no defect in rheumatoid arthritis or UC. The defect was corrected with exogenous IL-8, implying that neutrophil function is normal, and the abnormality was present regardless of CARD15 status. IL-8 is produced largely by macrophages, and cultured macrophages from Crohn’s disease were shown to secrete …