Too Little or Too Much?

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Science  03 Mar 2006:
Vol. 311, Issue 5765, pp. 1215
DOI: 10.1126/science.311.5765.1215a

Crohn's disease is a severe inflammation of the mucosa of the intestine and is prevalent in developed countries. Multiple predisposing and environmental factors—such as mutations in the protein NOD2, which recognizes bacterial cell wall components—appear to influence the onset and progression of the condition, and current thinking is that these factors conspire to stir up unwanted immune reactions to the microflora of the gut.

Marks et al. provide evidence that Crohn's may instead be more representative of immunodeficiency. Crohn's patients were found to have reduced neutrophil accumulation and interleukin-8 (IL-8) production at sites of tissue trauma in the intestine and the skin. The defect in IL-8 production was independent of NOD2 mutation, and macrophages from patients were impaired in generating IL-8 in response to wound fluid from healthy individuals. Skin responses to subcutaneous injection of killed bacteria were also diminished, with local blood flow in the patients less enhanced relative to that in healthy controls. This is consistent with a lower potential for acute inflammatory responses in Crohn's patients; thus, although Crohn's disease may culminate in a chronic inflammatory response, it may originate in deficient acute pro-inflammatory responses to bacteria. — SJS

Lancet 367, 668 (2006).

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