DIRECT EVIDENCE OF MONOCYTE RECRUITMENT TO INFLAMMATORY BOWEL-DISEASEMUCOSA

Alterations in phenotype and function of intestinal macrophages occur in inflammatory bowel disease (IBD) but it is unclear whether these ch anges result from the recruitment of circulating monocytes to the inte stine or from proliferation of resident intestinal macrophages. We sou ght to demonstrate the arrival of blood monocytes, the precursors of m acrophages, in IBD mucosa. Peripheral blood mononuclear cells were iso lated from 23 patients with clinically active intestinal inflammation (13 Crohn's disease, eight ulcerative colitis, two infective colitis), then radiolabelled with (99m)technetium (Tc)-stannous colloid (n=13) or (111)indium (In)-oxine (n=10) before re-injection and abdominal sca nning. Four patients had demonstrable intestinal monocyte uptake using [Tc-99m]-stannous colloid, while six [In-111]-oxine-labelled monocyte scans were positive. Uptake sites correlated with actively inflamed r egions. Patients demonstrating monocyte uptake had been treated with c orticosteroids for a significantly (P<0.02) shorter duration (median 3 vs 20 days) than those with negative scans. There was no significant difference between positive and negative scans for disease category, c linical or histological disease activity, or radioisotope used. Biopsi es of inflamed mucosa from two patients suffering ulcerative colitis w ho had positive scans showed a high proportion of CD14-positive macrop hages, 4-9% of which contained autoradiographic grains. These results demonstrate that blood monocytes are recruited to the mucosa of active ly inflamed bowel, and suggest that this process may be inhibited by c orticosteroids. Moreover, the phenotype of the recently-arrived monocy tes indicates their susceptibility to stimulation by lipopolysaccharid e, and suggests a mechanism for the continuing inflammation in the bac terial product-rich milieu of IBD.