Coordinate upregulation of interleukin-8 and growth-related gene product-α is present in the colonic mucosa of inflammatory bowel disease

˜-chemokines in the intestinal mucosa of patients with IBD. Methods: The contents of IL-8 and GRO a in organ cultures, the expression of IL-8 and GRO a mRNA, and the modulatory effects of ine ammatory mediators on IL-8 and GRO a-producing cells were examined using colonic mucosal tissues. In vitro stimulatory effects of IL-8 and GRO a on neutrophils were investigated in terms of chemotactic migration and superoxide anion generation. Results: The contents of IL-8 and GROa in organ cultures were elevated in patients with IBD, especially in those with active ulcerative colitis (UC). Both IL-8 and GRO a contents increased according to an increase in histological disease activity in patients with UC, but not in those with Crohn disease. In contrast, no signie cant correlation was found between the contents of these a-chemokines and clinical disease activity. In situ hybridization detected increased expression of IL-8 and GRO a mRNA in macrophages, pericrypt myoe broblasts, and the epithelium of tissue specimens with active lesions of IBD. The secretion of IL-8 and GRO a from macrophages and myoe broblasts obtained from control patients was upregulated by ine ammatory cytokines and bacterial products. The concentrations of recombinant (r)-IL-8, which covered the levels of activity detected in individual organ cultures or cell cultures of fractionated mucosal cells, could induce chemotactic migration and superoxide anion generation in neutrophils in vitro, and r-GRO a had synergistic effects on r-IL-8-induced neutrophil activation. Conclusions: A coordinate upregulation of IL-8 and GROa may be involved in the tissue injury in patients with IBD through their stimulatory effects on neutrophils.