Abstract | BACKGROUND: METHODS: RESULTS: In the placebo group, C5a and sC5b-9 levels increased by 37% (7.9-14.2 ηg/mL, P = .007) and 96% (442-845 ηg/mL, P < .0001), respectively, during the first 24 hours. Pexelizumab prevented the increase in C5a (P = .01 vs placebo), but not that of sC5b-9 (502-1,157 ηg/mL, not significant vs placebo). Levels of C-reactive protein, interleukin (IL) 6, IL-1ß, Regulated on Activation, Normal T Cell Expressed and Secreted ( RANTES) or Chemokine C-C motif ligand 5 (CCL5), and N-terminal probrain natriuretic peptide increased significantly in both groups; those of IL-10, IL-12, IL-1ra, and Interferon gamma-induced protein 10 (IP-10) or C-X-C motif chemokine 10 (CXCL10) decreased. Pexelizumab halved the increase in IL-6 (+92% vs 156%, P = .01) without effects on other markers, including C-reactive protein and N-terminal probrain natriuretic peptide. In cell culture, pexelizumab inhibited C5a, sC5b-9, and membrane-bound C5b-9 by 92%, 75%, and 78%, respectively (all P < .0001), without influencing cytokine levels and cell apoptosis. CONCLUSIONS: The blockage of both C5a and terminal complement in cell culture, but of C5a only in vivo with minimal effects on inflammation and risk biomarkers, supports the hypothesis that late administration of pexelizumab after the ischemia/reperfusion insult precluded adequate myocardial protection, resulting in a negative trial.
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Authors | Catherine Martel, Christopher B Granger, Marta Ghitescu, Amanda Stebbins, Annik Fortier, Paul W Armstrong, Arnaud Bonnefoy, Pierre Theroux |
Journal | American heart journal
(Am Heart J)
Vol. 164
Issue 1
Pg. 43-51
(Jul 2012)
ISSN: 1097-6744 [Electronic] United States |
PMID | 22795281
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Mosby, Inc. All rights reserved. |
Chemical References |
- Antibodies, Monoclonal, Humanized
- Complement Membrane Attack Complex
- Single-Chain Antibodies
- pexelizumab
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Topics |
- Aged
- Angioplasty, Balloon, Coronary
- Antibodies, Monoclonal, Humanized
(therapeutic use)
- Complement Membrane Attack Complex
(antagonists & inhibitors)
- Double-Blind Method
- Female
- Humans
- Male
- Middle Aged
- Myocardial Infarction
(therapy)
- Prospective Studies
- Single-Chain Antibodies
(therapeutic use)
- Treatment Failure
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