Effects of low dose intra-arterial monoclonal antibodies to ICAM-1 and CD11/CD18 on local and systemic consequences of ischaemia-reperfusion injury in skeletal muscle

Abstract

The aim of this study was to investigate the effects of intra-arterial infusion of low doses of monoclonal antibodies (Mabs) against adhesion molecules (the neutrophil CD18 integrins, and the endothelial adhesion molecule, ICAM-1) on reperfusion injury in skeletal muscle. The rabbit rectus femoris muscle was rendered ischaemic for 22 1 hours. Mabs were infused (−0.5 mg/kg) commencing 20 minutes before the end of ischaemia and for the first hour of reperfusion. 24 hours after reperfusion, the muscle was assessed for viability, oedema and neutrophil infiltration (myeloperoxidase (MPO) levels). The results of the viability assessment (control—20.9 (0–47.5)% [median (range)], anti-CD18 — 30.5 (3.0–89.4)%, anti-ICAM-1 — 27.9 (7.8—78.1)% and anti-CD18 combined with anti-ICAM-1 — 45.2 (15.6–92.3)%) showed no significant differences between groups, while analysis of MPO in the postischaemic muscle showed that the anti-ICAM-1 Mab reduced neutrophil infiltration significantly. Furthermore, in contralateral unoperated muscles MPO levels were elevated 24 hours after ischaemia in the contralateral muscle. This increased neutrophil infiltration was prevented by pretreatment with anti-ICAM-1. These results suggest that low doses of anti-CD18 and anti-ICAM-1 Mabs do not reduce reperfusion injury in skeletal muscle but may help to protect against systemic effects of severe trauma. The evidence suggests that reperfusion injury in this skeletal muscle model may be largely independent of neutrophil involvement.