IL-8 as an important chemoattractant for neutrophils in ulcerative colitis and Crohn's disease

Abstract

SUMMARYIL-8 is generating increasing interest as a powerful neutrophil chemoattractant and activator. To elucidate the mechanisms of neutrophil infiltration in inflammatory bowel disease, we examined 33 patients with ulcerative colitis (UC), 18 with Crohn's disease (CD), eight with some other type of colitis, and 18 normal control subjects for measurement of IL-8 in homogenates of colonic biopsy specimens. The affected colonic mucosa was found to contain significantly more IL-8 in patients with active inflammatory bowel disease than in patients with inactive disease (UC, P<0-001; CD, P < 0-001), in patients with other types of colitis (UC, P < 0 05; CD, P < 0-0 1), or in normal control subjects (UC, P<0-001; CD, P<0-001). Colonic IL-8 levels correlated significantly with the macroscopic grade of local inflammation, especially in patients with UC (P< 0-001). Colonic IL-8 levels also correlated well with the neutrophil numbers in mucosal tissue (UC, r = 0-950, P <0-001; CD, r = 0 940, P < 0-001), and with colonic IL-1I (r = 0-91 1, P < 0-001) and tumour necrosis factoralpha (TNF-a) levels (r = 0-604, P < 0-001 ) in patients with these two conditions. These data suggest a potential role for IL-8 and its regulatory cytokines IL-1 and TNF-a in mediating neutrophil infiltration of the gut wall in inflammatory bowel disease.

Prostaglandin E2 modulates IL‐8 expression through formation of a multiprotein enhanceosome in human colonic epithelial cells

“…IL-8 is a major pro-inflammatory cytokine belonging to the CXC chemokine family. IL-8 was originally identified as a neutrophil chemoattractant and activator which may cause non-specific tissue damage and promote inflammation [7]. Along with chemotaxis, it can also induce activation of target cells by increasing intracellular Ca 2+ and respiratory burst.…”

Osteoblast retraction induced by adherent neutrophils promotes osteoclast bone resorption: implication for altered bone remodeling in chronic gout

“…7 IL-8 is a chemokine that attracts and activates neutrophils, the major cell type involved in gouty arthritis. 8,9 Neutrophils and their precursors are abundantly present in bone marrow. Interestingly, bone marrow neutrophilia induced by IL-6 was shown to be associated with important histological modifications of bone like low number of OBs and reduction of bone turnover.…”

Cellular Infiltration and Cytokine Expression Correlate with Fistulizing State in Crohn's Disease

“…Macrophages in CD patients have been shown to express an activated phenotype (CD14 ϩ ) that is not normally expressed in a healthy intestine (17). Furthermore, mechanisms involved in recruiting and activating inflammatory cells are thought to involve a complex interplay of inflammatory mediators such as chemokines and cytokines (9).…”