Amelioration of graft versus host disease with anti-ICAM-1 therapy

We have previously demonstrated an increase in the adhesion molecule lymphocyte function-associated antigen-1 (LFA-1) in GVHD after small bowel transplantation (SBTx) and a therapeutic effect for the monoclonal antibody (MoAb) to LFA-1 in the same model. The present study evaluated the role of MoAb to LFA-1's ligand, intercellular adhesion molecule-1 (ICAM-1) in GVHD. Methods. GVHD was created in LBNF₁ rats by heterotopic vascularized SBTx from Lewis donors. Saline treated SBTx-GVHD and sham-operated control animals were compared to animal groups treated with MoAb to ICAM-1 or MoAb to ICAM-1 and LFA-1. GVHD was evaluated by measuring spleen index, white blood cell count, bowel permeability, weight loss, and animal survival. Results. Animals treated with the MoAb to ICAM-1 appeared clinically to have almost as severe GVHD as untreated animals; however, they had improved spleen indices, less neutropenia and weight loss, and survived longer than untreated animals (range 15-22 days in treated animals vs 12-16 days in untreated animals, P < 0.01). Treatment with MoAb to both ICAM-1 and LFA-1 appeared to have a synergistic beneficial effect on GVHD (range 19-29 days, P < 0.001 vs untreated animals). Conclusion. MoAb to ICAM-1 alone or in combination with MoAb to LFA-1 ameliorates GHVD after SBTx and prolongs survival.