MIPSA: Monocyte Profiles in Critically Ill Patients With Pseudomonas Aeruginosa Sepsis
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
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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 Design
Outcome Measures
Primary Outcome Measures
- Monocyte surface marker expression in critically ill patients with Pseudomonas aeruginosa sepsis [two years]
Monocyte type 1, type 2 surface marker expression
Secondary Outcome Measures
- Cytokine concentrations in serum and production after ex-vivo stimulation of isolated monocytes of critically ill patients with Pseudomonas aeruginosa sepsis with LPS [four years]
IL-8 and IFN-gamma
Eligibility Criteria
Criteria
Inclusion Criteria:
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age > 18 years
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critically ill patients with sepsis
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microbiologically proven infection with Pseudomonas aeruginosa
Exclusion Criteria:
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life expectancy < 24 hours
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participation in other studies
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinic of Anesthesiology | Ulm | Germany | 89070 |
Sponsors and Collaborators
- 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
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003 Jan 9;348(2):138-50. Review.
- Mantovani A, Sica A, Locati M. New vistas on macrophage differentiation and activation. Eur J Immunol. 2007 Jan;37(1):14-6. Review.
- PSA_Sepsis_M_1_2