The role of CCL3/macrophage inflammatory protein-1alpha in experimental colitis.

CCL3/macrophage inflammatory protein (MIP-1)-1alpha is elevated in the rectal biopsies of patients with active inflammatory bowel diseases, but its role remains undefined. The present study examined the role of CCL3/MIP-1alpha during trinitrobenzene sulfonic acid (TNBS)-induced colitis in the rat. Colonic CCL3/MIP-1alpha levels were elevated (>20-fold above control) within 24 h and remained elevated to day 7 of colitis induction by TNBS administration. In addition, significant increases in colonic neutrophil accumulation were observed within 24 h to day 7 of TNBS treatment. Pre-treatment of rats with a single dose of CCL3/MIP-1alpha antibody significantly reduced (47%) colonic neutrophil accumulation during the early (24 h) phase of TNBS-induced colitis. In contrast, chronic (repeated) administration of CCL3/MIP-1alpha antibody did not attenuate colonic neutrophil accumulation during the late phase (day 7) of TNBS-induced colitis. These results suggest a role for CCL3/MIP-1alpha in promoting colonic neutrophil accumulation during the early (24 h) phase of TNBS-induced colitis.