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. 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.
Saville
L R
LR
Spinal Cord Injury Team, BioTherapeutics Research Group, Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada.
Pospisil
C H
CH
Mawhinney
L A
LA
Bao
F
F
Simedrea
F C
FC
Peters
A A
AA
O'Connell
P J
PJ
Weaver
L C
LC
Dekaban
G A
GA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000378:metabolism / Q000627:therapeutic use*; D018845:CD11 Antigens / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D003429:Cross Reactions; D005260:Female; D006801:Humans; D039001:Integrin alpha Chains / Q000276:immunology* / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D009187:Myelitis / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000276:immunology / Q000378:metabolism / Q000628:therapy*
D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; C406812:ITGAD protein, human; D039001:Integrin alpha Chains; D018696:Neuroprotective Agents