AUGMENTED PASSIVE IMMUNOTHERAPY WITH P4 PEPTIDE IMPROVES PHAGOCYTE ACTIVITY IN SEVERE SEPSIS

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Morton, B, Mitsi, E, Pennington, SH, Reine, J, Wright, AD, Parker, R, Welters, ID ORCID: 0000-0002-3408-8798, Blakey, JD, Rajam, G, Ades, EW et al (show 4 more authors) , Ferreira, DM, Wang, D, Kadioglu, A ORCID: 0000-0003-1137-6321 and Gordon, SB (2016) AUGMENTED PASSIVE IMMUNOTHERAPY WITH P4 PEPTIDE IMPROVES PHAGOCYTE ACTIVITY IN SEVERE SEPSIS SHOCK, 46 (6). pp. 635-641. ISSN 1073-2322, 1540-0514

Text Augmented Passive Immunotherapy with P4 Peptide Improves Phagocyte Activity in Severe Sepsis.pdf - Author Accepted Manuscript Download (340kB)

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:	24 Jun 2026 19:59
DOI:	10.1097/SHK.0000000000000715
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3006274
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