Monocyte Profiles in Critically Ill Patients With Pseudomonas Aeruginosa Sepsis (MIPSA)

Phenotypical Und Functional Characterization of Macrophages in Critically Ill Patients With Pseudomonas Aeruginosa Induced Sepsis

The present study focuses on patients with Pseudomonas aeruginosa (PSA) sepsis. The aim of the present study is to find out whether the M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotype predominates in blood monocytes in critically ill patients with PSA-sepsis, and whether the severity of sepsis and outcome is associated with distinct monocyte phenotype and function.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Critically Ill; Pseudomonas Infections; Sepsis, Severe; Pseudomonas Septicemia; Pseudomonas; Pneumonia; Pseudomonal Bacteraemia; Pseudomonas Urinary Tract Infection; Pseudomonas Gastrointestinal Tract Infection

Detailed Description

During bacterial related sepsis, one of the key playing cells are macrophages, monocytes and T-lymphocytes (Hotchkiss et al., 2003). Macrophages and monocytes are supposed to be essential for the septic reaction to Gram-negative bacteria (Hotchkiss et al. 2003). Generally, there are two dominant types of macrophages: the pro-inflammatory M1 macrophage and the anti-inflammatory M2 macrophage (Mantovani et al., 2006). Similar to this macrophage characteristics, monocytes can also be categorized into pro-or anti-inflammatory. These macrophage/monocyte phenotypes can be differentiated in vitro from freshly isolated human blood monocytes using either GM-CSF giving raise to M1 macrophage/monocyte or M-CSF resulting in M2 macrophage/monocyte (Mantovani et al., 2006; Neu et al., 2013). Brunialti et al. (2012) have already demonstrated that the population of antiinflammatory M2 monocytes in septic patients is bigger than the pro-inflammatory M1 population. However, the authors did not further analyze the underlying mechanisms of M2 polarization nor did they identify the sepsis-causing pathogens.

In the present study, monocytes and macrophages of patients with Pseudomonas aeruginosa (PSA) sepsis are characterized by their surface marker expression profile via flow cytometry and cytokine pattern by ELISA in vivo and after ex-vivo LPS stimulation. In addition, an ex-vivo model system for PSA induced sepsis is validated. Blood of critically ill patients in the ICU infected with PSA is sampled to isolate peripheral blood mononuclear cells (PBMCs). Blood monocytes are analyzed for surface marker expression to determine the relative proportions of M1 and M2 monocytes in these patients and in healthy controls by flow cytometry

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Manfred Weiss, MD, MBA; Phone Number: +49 731 500 60226; Email: manfred.weiss@uniklinik-ulm.de
• Study Contact Backup: Name: Eberhard Barth, MD; Phone Number: +49 731 500 60050; Email: eberhard.barth@uniklinik-ulm.de

Study Locations

• Germany
  • Ulm, Germany, 89070
    • Recruiting
    • Clinic of Anesthesiology
    • Contact: Eberhard Barth, MD; Phone Number: +49-(0)731-500-60050; Email: eberhard.barth@uniklinik-ulm.de
    • Sub-Investigator: Michael Goergieff, MD
    • Sub-Investigator: Hendrik Bracht, MD
    • Sub-Investigator: Florian Gebhard, MD
    • Sub-Investigator: Doris Henne-Bruns, MD
    • Sub-Investigator: Marc-Eric Halatsch, MD
    • Sub-Investigator: Karl-Heinz Orend, MD
    • Sub-Investigator: Andreas Essig, MD
    • Sub-Investigator: Christian Riedel, PhD
    • Principal Investigator: Anne Sedlag, Biochemist
    • Contact: Manfred Weiss, MD, MBA; Phone Number: +49-(0)731-500-60226; Email: manfred.weiss@uniklinik-ulm.de
    • Sub-Investigator: Eberhard Barth, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Critically ill patients with sepsis with microbiologically proven infection with Pseudomonas aeruginosa

Description

Inclusion Criteria:

• age > 18 years
• critically ill patients with sepsis
• microbiologically proven infection with Pseudomonas aeruginosa

Exclusion Criteria:

• life expectancy < 24 hours
• participation in other studies

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monocyte surface marker expression in critically ill patients with Pseudomonas aeruginosa sepsis	Monocyte type 1, type 2 surface marker expression	two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cytokine concentrations in serum and production after ex-vivo stimulation of isolated monocytes of critically ill patients with Pseudomonas aeruginosa sepsis with LPS	IL-8 and IFN-gamma	four years

Collaborators and Investigators

• Sponsor: University of Ulm
• Investigators: Principal Investigator: Manfred Weiss, MD, MBA, University Ulm, University Hospital Ulm; Principal Investigator: Anne Sedlag, Biochemist, University Ulm, Institute of Microbiology and Biotechnology

Publications and helpful links

General Publications

• Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003 Jan 9;348(2):138-50. doi: 10.1056/NEJMra021333. No abstract available.
• Brunialti MK, Santos MC, Rigato O, Machado FR, Silva E, Salomao R. Increased percentages of T helper cells producing IL-17 and monocytes expressing markers of alternative activation in patients with sepsis. PLoS One. 2012;7(5):e37393. doi: 10.1371/journal.pone.0037393. Epub 2012 May 31.
• Mantovani A, Sica A, Locati M. New vistas on macrophage differentiation and activation. Eur J Immunol. 2007 Jan;37(1):14-6. doi: 10.1002/eji.200636910.
• Neu C, Sedlag A, Bayer C, Forster S, Crauwels P, Niess JH, van Zandbergen G, Frascaroli G, Riedel CU. CD14-dependent monocyte isolation enhances phagocytosis of listeria monocytogenes by proinflammatory, GM-CSF-derived macrophages. PLoS One. 2013 Jun 11;8(6):e66898. doi: 10.1371/journal.pone.0066898. Print 2013.

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: February 2, 2017
• First Submitted That Met QC Criteria: February 2, 2017
• First Posted (Estimated): February 6, 2017

Study Record Updates

• Last Update Posted (Actual): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: sepsis; cytokine; critically ill patient; macrophage; severity of disease; monocyte; pseudomonas aeruginosa
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Sepsis; Toxemia; Infections; Communicable Diseases; Bacteremia; Urinary Tract Infections; Critical Illness; Pseudomonas Infections
• Other Study ID Numbers: PSA_Sepsis_M_1_2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO