Neutrophils are important cellular mediators in inflammatory bowel dis
ease (IBD). Interleukin (IL)8, a powerful neutrophil chemoattractant,
is found in increased quantities in inflamed mucosa, but the cells of
origin are uncertain. IL8 gene expression was studied by in situ hybri
disation in uninflamed intestinal tissue resected for colon carcinoma
(n=7) and in inflamed colonic tissue resected for IBD (n=11). Immunohi
stochemistry was used to assess the phenotype of IL8 expressing macrop
hages and the production of IL8 protein. Macrophages isolated from int
estinal resections and lipopolysaccharide stimulated peripheral blood
monocytes treated with 5-aminosalicylic acid, hydrocortisone, and cycl
osporin A were examined for IL8 mRNA by northern blotting and IL8 secr
etion by enzyme linked immunosorbent assay (ELISA). In all cases IL8 m
RNA was detected by in situ hybridisation in macrophages and neutrophi
ls adjacent to ulceration in inflamed bowel, but not detected in uninf
lamed carcinoma resections. recruited CD14 positive macrophages were r
esponsible for some of this IL8 expression. IL8 protein was present in
the same distribution as mRNA. Epithelial cells in normal and inflame
d tissue showed neither mRNA nor protein. IL8 mRNA was expressed signi
ficantly more commonly by macrophages from IBD affected than from norm
al mucosa, and IL8 secretion by IBD but not normal colon macrophages w
as augmented significantly by lipopolysaccharide treatment, IL8 expres
sion and production by lipopolysaccharide treated blood monocytes was
inhibited by the therapeutic agents tested. These results show that ne
utrophils and recently recruited macrophages are responsible for produ
ction of IL8 in IBD, suggesting a mechanism for a continuing cycle of
neutrophil attraction. Agents used therapeutically in these diseases m
ay be effective in part by disrupting this cycle.