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Augmented Passive Immunotherapy with P4 Peptide Improves Phagocyte Activity in Severe Sepsis

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Morton, Ben ORCID: https://orcid.org/0000-0002-6164-2854, Mitsi, Elena, Pennington, Shaun ORCID: https://orcid.org/0000-0002-7160-6275, Reiné, Jesús, Wright, Angela, Parker, Robert, Welters, Ingeborg D, Blakey, John, Rajam, Gowrisankar, Ades, Edwin W, Ferreira, Daniela ORCID: https://orcid.org/0000-0001-7730-9477, Wang, Duolao ORCID: https://orcid.org/0000-0003-2788-2464, Kadioglu, Aras and Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116 (2016) 'Augmented Passive Immunotherapy with P4 Peptide Improves Phagocyte Activity in Severe Sepsis'. Shock, Vol 46, Issue 6, pp. 635-641.

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Abstract

INTRODUCTION
Antimicrobial resistance threatens to undermine treatment for severe infection; new therapeutic strategies are urgently needed. Pre-clinical 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 post discharge). Blood samples were taken in early (≤ 48hrs post-diagnosis, n = 54), latent (seven days post-diagnosis, n = 39) and convalescent (3-6 months post-diagnosis, n = 18) phases of disease. The primary outcome measure was killing of opsonised S.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 opsonised pneumococci by 8.6% (C.I. 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 to 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 pre-clinical 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
Subjects: QU Biochemistry > Proteins. Amino Acids. Peptides > QU 68 Peptides
QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified.
WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases
WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 240 Bacteremia. Sepsis. Toxemias
Faculty: Department: Biological Sciences > Vector Biology Department
Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1097/SHK.0000000000000715
Depositing User: Jessica Jones
Date Deposited: 11 Oct 2016 13:02
Last Modified: 16 Oct 2017 11:23
URI: https://archive.lstmed.ac.uk/id/eprint/6258

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