CUTTING EDGE - CURATIVE TREATMENT OF AN EXPERIMENTALLY-INDUCED COLITIS BY A CD44 VARIANT V7-SPECIFIC ANTIBODY

Inflammatory bowel disease is a quite severe chronic inflammation, tre ated mainly by immunosuppression, which often has serious side effects . As CD44 is important in lymphocyte activation and migration, we aske d whether Abs against CD44 isoforms influence trinitrobenzenesulfonic acid (TNBS)-induced colitis in mice. A lethal colitis (73/111 mice) co uld be prevented in 69 of 97 mice by anti-CD44v7 (CD44 variant isoform v7), whereas anti-CD44s (CD44 standard isoform) and anti-CD44v6 had n o effect. Upon receiving anti-CD44v7 after the disease had been fully exacerbated, >90% of the mice recovered. TNBS plus anti-CD44v7-treated mice developed early signs of inflammation, with infiltration of leuk ocytes in the lamina propria and increased IFN-gamma production. Howev er, while control mice developed a severe pancolitis, the intestine fu lly regenerated in anti-CD44v7-treated mice. Locally and systemically, a strong increase in IL-10 production was noted, Thus, anti-CD44v7 ca n be regarded as a highly efficient and specific therapeutic reagent i n chronic colitis, which probably functions by regulating an overshoot ing Th1 reaction.