Monocyte Profiles in Critically Ill Patients With Pseudomonas Aeruginosa Sepsis

Sepsis Clinical Trial

— MIPSA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03044223
• Other study ID #: PSA_Sepsis_M_1_2
• Status: Recruiting
• Start date: August 2014
• Est. completion date: December 2026

Study information

• Verified date: January 2024
• Source: University of Ulm
• Contact: Manfred Weiss, MD, MBA
• Phone: +49 731 500 60226
• Email: manfred.weiss[@]uniklinik-ulm.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2026
• Est. primary completion date: November 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Bacteremia
• Communicable Diseases
• Critical Illness
• Critically Ill
• Infections
• Pseudomonal Bacteraemia
• Pseudomonas Gastrointestinal Tract Infection
• Pseudomonas Infections
• Pseudomonas Septicemia
• Pseudomonas Urinary Tract Infection
• Pseudomonas; Pneumonia
• Sepsis
• Sepsis, Severe
• Toxemia
• Urinary Tract Infections

Locations

Country	Name	City	State
Germany	Clinic of Anesthesiology	Ulm

Sponsors (1)

Lead Sponsor	Collaborator
University of Ulm

Country where clinical trial is conducted

Germany, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Monocyte surface marker expression in critically ill patients with Pseudomonas aeruginosa sepsis	Monocyte type 1, type 2 surface marker expression	two years
Secondary	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