Monocyte Profiles in Critically Ill Patients With Pseudomonas Aeruginosa Sepsis

NCT ID: NCT03044223

Last Updated: 2024-01-17

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-08-31
• Study Completion Date: 2026-12-31

Brief Summary

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.

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

Conditions

Pseudomonas Infections; Pseudomonas Septicemia; Pseudomonas; Pneumonia; Pseudomonal Bacteraemia; Pseudomonas Urinary Tract Infection; Pseudomonas Gastrointestinal Tract Infection; Sepsis; Sepsis, Severe; Critically Ill

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Ulm

OTHER

Sponsor Role: lead

Responsible Party

Manfred Weiss

Professor, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Manfred Weiss, MD, MBA

Role: PRINCIPAL_INVESTIGATOR

University Ulm, University Hospital Ulm

Anne Sedlag, Biochemist

Role: PRINCIPAL_INVESTIGATOR

University Ulm, Institute of Microbiology and Biotechnology

Locations

Clinic of Anesthesiology

Ulm, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Manfred Weiss, MD, MBA

Role: CONTACT

manfred.weiss@uniklinik-ulm.de

+49 731 500 60226

Eberhard Barth, MD

Role: CONTACT

eberhard.barth@uniklinik-ulm.de

+49 731 500 60050

Facility Contacts

Manfred Weiss, MD, MBA

Role: primary

manfred.weiss@uniklinik-ulm.de

+49-(0)731-500-60226

Eberhard Barth, MD

Role: backup

eberhard.barth@uniklinik-ulm.de

+49-(0)731-500-60050

References

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.

Reference Type: BACKGROUND

PMID: 22693573 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12519925 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17183610 (View on PubMed)

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.

Reference Type: RESULT

PMID: 23776701 (View on PubMed)

Other Identifiers

PSA_Sepsis_M_1_2

Identifier Type: -

Identifier Source: org_study_id