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Article type: Research Article
Authors: Fox, Douglas J. | Doolabh, Vaishali B. | Mackinnon, Susan E. | Genden, Eric M. | Hunter, Daniel A.
Affiliations: Department of Surgery, Division of Plastic Surgery, Washington University School of Medicine, St. Louis, MO, USA | Department of Otolaryngology, Mount Sinai School of Medicine, New York, NY, USA
Note: [] NRSA IF32NS10254 02 National Institute of Neurological Disorders and Stroke. Plastic Surgery Education Foundation Fellowship.
Note: [] Corresponding author: One Barnes-Jewish Hospital Plaza, Suite 17424 East Pavilion, St. Louis, MO 63110, USA. Tel.: +1 314 362-4586; Fax: +1 314 362-4536; E-mail: [email protected].; NIH R01NS33406-03.
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-1 ) 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 combi-nation 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.
Keywords: ICAM-1, LFA-1, peripheral nerve allograft, Cyclosporin A, monoclonal antibody, adhesion molecules
Journal: Restorative Neurology and Neuroscience, vol. 15, no. 4, pp. 319-326, 1999
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