CXCR1‐binding chemokines in inflammatory bowel diseases: down‐regulated IL‐8/CXCL8 production by leukocytes in Crohn's disease and selective GCP‐2/CXCL6 expression in inflamed intestinal tissue

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Abstract
Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that are characterized by chronic intestinal inflammation and a constant influx of leukocytes mediated by pro‐inflammatory cytokines and chemokines. The intestinal expression of the CXCR1‐binding chemokines IL‐8/CXCL8 and GCP‐2/CXCL6 and the participation of immunocompetent cells in IBD were evaluated. IL‐8 production by peripheral blood mononuclear cells (PBMC) from IBD patients, stimulated with endotoxin, plant lectin or double‐stranded RNA, was significantly lowered in patients with CD, but not in UC patients or healthy subjects. The reduced chemokine production by PBMC from IBD patients was both IL‐8 and CD specific, but not inducer dependent. In serum, most chemokines remained undetectable, while the levels of those that were measurable remained unaltered in IBD patients. GCP‐2, but not ENA‐78/CXCL5, nor IL‐8, were highly expressed by endothelial cells in inflamed intestinaltissue of IBD patients. In contrast, stimulated endothelial cell cultures produced more IL‐8 than GCP‐2. The selective GCP‐2 staining of endothelial cells at sites of ulcerations suggests that GCP‐2, despite its low production capacity in vitro, plays a role in IBD that is different from that of structurally (ENA‐78) and functionally (IL‐8) related ELR+ CXC chemokines. Thus, the chemokine network shows complementarity rather than redundancy.