A monoclonal antibody to CD11d reduces the inflammatory infiltrate into the injured spinal cord: a potential neuroprotective treatment

A monoclonal antibody to CD11d reduces the inflammatory infiltrate into the injured spinal cord: a potential neuroprotective treatment

The accumulation of inflammatory cells in the lesion of a spinal cord injury (SCI) enhances secondary damage, resulting in further neurological impairment. High-dose methylprednisolone (MP) treatment is the only accepted treatment for inflammation secondary to human SCI but is minimally effective. U...

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Bibliographic Details
Published in:Journal of neuroimmunology Vol. 156; no. 1; pp. 42 - 57
Main Authors: Saville, L.R., Pospisil, C.H., Mawhinney, L.A., Bao, F., Simedrea, F.C., Peters, A.A., O'Connell, P.J., Weaver, L.C., Dekaban, G.A.
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01-11-2004
Subjects:
Animals
Antibodies, Monoclonal - biosynthesis
Antibodies, Monoclonal - metabolism
Antibodies, Monoclonal - therapeutic use
CD11 Antigens - immunology
CD11 Antigens - metabolism
CD11dCD18
Cell Movement - immunology
Cross Reactions
Female
Humans
Inflammation
Integrin alpha Chains - immunology
Integrin alpha Chains - metabolism
Leukocytes - immunology
Leukocytes - metabolism
Methylprednisolone
Myelitis - immunology
Myelitis - metabolism
Myelitis - prevention & control
Neuroprotective Agents - pharmacology
Rats
Rats, Wistar
Spinal Cord Injuries - immunology
Spinal Cord Injuries - metabolism
Spinal Cord Injuries - therapy
Spinal cord injury
β 2 integrin
Inflammation
CD11dCD18
Spinal cord injury
Methylprednisolone
β 2 integrin
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Summary:The accumulation of inflammatory cells in the lesion of a spinal cord injury (SCI) enhances secondary damage, resulting in further neurological impairment. High-dose methylprednisolone (MP) treatment is the only accepted treatment for inflammation secondary to human SCI but is minimally effective. Using a rat SCI model, we devised an anti-inflammatory treatment to block the infiltration of neutrophils and hematogenous monocyte/macrophages over the first 2 days postinjury by targeting the CD11dCD18 integrin. Anti-CD11d mAb administration following SCI effectively reduced neutrophil and macrophage infiltrate into lesions by 70% and 36%, respectively, over the first 72 h post-SCI. MP also reduced neutrophil and macrophage infiltrate by 60% and 28%, respectively, but by different mechanisms. The immunosuppression caused by anti-CD11d treatment was not sustained, as inflammatory cell numbers were not different from those observed in untreated SCI control animals at 7 days postinjury. In contrast, in MP-treated animals, the number of macrophages was still suppressed in the lesion while neutrophil numbers were significantly increased. These results suggest that anti-CD11d mAb treatment following SCI will minimize the destructive actions associated with early, uncontrolled leukocyte infiltration into the lesion while permitting the positive wound healing effects of macrophages at later time points.
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ISSN:0165-5728
1872-8421
DOI:10.1016/j.jneuroim.2004.07.002