Morton, B 
ORCID: 0000-0002-6164-2854, Mitsi, E, Pennington, SH, Reine, J, Wright, AD, Parker, R, Welters, ID ORCID: 0000-0001-8734-994X, Blakey, JD ORCID: 0000-0003-2551-8984, Rajam, G, Ades, EW et al (show 4 more authors)
(2016)
AUGMENTED PASSIVE IMMUNOTHERAPY WITH P4 PEPTIDE IMPROVES PHAGOCYTE ACTIVITY IN SEVERE SEPSIS.
SHOCK, 46 (6).
pp. 635-641.
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Augmented Passive Immunotherapy with P4 Peptide Improves Phagocyte Activity in Severe Sepsis.pdf - Author Accepted Manuscript Download (340kB) |
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Abstract
Introduction: Antimicrobial resistance threatens to undermine treatment of severe infection; new therapeutic strategies are urgently needed. Preclinical work shows that augmented passive immunotherapy with P4 peptide increases phagocytic activity and shows promise as a novel therapeutic strategy. Our aim was to determine ex vivo P4 activity in a target population of patients admitted to critical care with severe infection. Methods: We prospectively recruited UK critical care unit patients with severe sepsis and observed clinical course (≥3 months postdischarge). Blood samples were taken in early (≤48 h postdiagnosis, n = 54), latent (7 days postdiagnosis, n = 39), and convalescent (3–6 months postdiagnosis, n = 18) phases of disease. The primary outcome measure was killing of opsonized Streptococcus pneumoniae by neutrophils with and without P4 peptide stimulation. We also used a flow cytometric whole blood phagocytosis assay to determine phagocyte association and oxidation of intraphagosomal reporter beads. Results: P4 peptide increased neutrophil killing of opsonized pneumococci by 8.6% (confidence interval 6.35–10.76, P < 0.001) in all phases of sepsis, independent of infection source and microbiological status. This represented a 54.9% increase in bacterial killing compared with unstimulated neutrophils (15.6%) in early phase samples. Similarly, P4 peptide treatment significantly increased neutrophil and monocyte intraphagosomal reporter bead association and oxidation, independent of infection source. Conclusions: We have extended preclinical work to demonstrate that P4 peptide significantly increases phagocytosis and bacterial killing in samples from a target patient population with severe sepsis. This study supports the rationale for augmented passive immunotherapy as a therapeutic strategy in severe sepsis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Bacterial infection, innate immunity, neutrophil biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 09 Mar 2017 10:37 |
| Last Modified: | 19 Jan 2023 07:14 |
| DOI: | 10.1097/SHK.0000000000000715 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3006274 |
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