ANTI-CD11B CD18 ANTIBODIES REDUCE INFLAMMATION IN ACUTE COLITIS IN RATS/

The influx of monocytes and neutrophils into the inflamed tissue could be an important aspect in the pathogenesis of inflammatory bowel dise ase (IBD). A membrane protein involved in the monocyte/neutrophil adhe rence to endothelium is CD1b/CD18 or alpha M beta(2) (complement recep tor type 3 = CR3). In the present study the role of CD 11b/CD18 in exp erimental IBD was studied by treatment with ED7 and OX42, two MoAbs ag ainst CD11b/CD18. Colitis was induced in rats by a single, rectal admi nistration of 30 mg 2,4,6-trinitrobenzene sulfonic acid (TNBS) dissolv ed in ethanol 30%. Two hours before and 3 days after induction of coli tis, the animals were given an i.v. dose of 0.5 mg of either ED7 or OX 42 in 1 ml PBS. Controls received PBS or an irrelevant MoAb. Four days after the last treatment with the antibodies, the rats were killed, a nd macroscopic damage scores of the colon were determined. Macrophages and granulocytes were studied by immunohistochemistry and quantified by Interaktives Bild Analysen System (IBAS), and myeloperoxidase (MPG) activity in colonic tissue was measured. After treatment with ED7 and OX42 the mean damage score of the colon was reduced from 4.2 in IBD a nimals to 1.0 and 1.3, respectively. Smaller areas of ulcerations and a decrease in the number of ulcerations were observed compared with PB S-treated rats. Furthermore, the amount of infiltrating monocytes and leucocytes in the submucosa was enormously reduced, as well as MPO act ivity in the colonic tissue. These results show that treatment with Mo Abs against CD11b/CD18 reduces clinical signs of experimental IBD in r ats by a partial blockade of infiltrating macrophages and granulocytes .