Decreased cyclosporin A requirement with anti-ICAM-1 and anti-LFA-1α in a peripheral nerve allotransplantation model

D. J. Fox, V. B. Doolabh, S. E. Mackinnon, E. M. Genden, D. A. Hunter

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Object: This study evaluated the dose related effects of Cyclosporin A (CsA) alone and in combination with monoclonal antibodies (mAbs) directed against intercellular adhesion molecule-1 (ICAM-1) and the alpha subunit of leukocyte function-associated antigen (LFA-1α) on peripheral nerve allograft rejection in a rat model. Methods: Nerve regeneration was assessed using gait analysis of returning hind limb function, histology, and morphometry. Results: Regeneration comparable to isograft controls and high dose CsA treatment groups was observed when mAbs were used in combination with intermediate dose CsA. Intermediate dose CsA therapy without additional mAbs was insufficient to support this level of regeneration. Nerve allografts treated with high and low dose CsA demonstrated no increased benefit with the addition of mAb therapy. Conclusions: Thus, mAbs seem to have a dose dependent effect on immunosuppression when used in combination with CsA, and may have therapeutic promise as a rescue therapy when CsA levels fall or issues of toxicity become important.

Original languageEnglish
Pages (from-to)319-326
Number of pages8
JournalRestorative Neurology and Neuroscience
Volume15
Issue number4
StatePublished - Dec 1 1999
Externally publishedYes

Keywords

  • Adhesion molecules
  • Cyclosporin A
  • ICAM-1
  • LFA-1
  • Monoclonal antibody
  • Peripheral nerve allograft

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