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.
Poritz
L S
LS
Department of Sugery, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania, 17033-0850, USA.
Page
M J
MJ
Tilberg
A F
AF
Koltun
W A
WA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D007421:Intestine, Small / Q000473:pathology / Q000503:physiopathology / Q000637:transplantation*; D007958:Leukocyte Count; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism; D008297:Male; D010539:Permeability; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013154:Spleen / Q000473:pathology; D014184:Transplantation, Homologous; D015431:Weight Loss
D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1