Innate Immune Functions of Immature Neutrophils

NCT01155674 | Unknown

• 1 other identifier: CER 09-311
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Polymorphonuclear neutrophils, or granulocytes, are essential effector cells of the innate immune system against bacterial infections. Their role in sepsis has been long established as the primary phagocyte to clear the infectious process. In the early phase of sepsis, one observes a massive recruitment of immature neutrophils from the bone marrow into peripheral blood, the so-called "band forms" or "left shift cells". Despite the daily clinical use of neutrophil band forms count in the care of septic patients and their abundance in septic blood, no information exists on the fate of these cells, nor on their capacity to mount an efficient innate immune response. It is the goal of this proposal to study the fate and the innate immune functions of immature neutrophils obtained in patients with early septic shock. Immature neutrophils will be separated from mature neutrophils. The following functions will be studied ex vivo in mature vs. immature neutrophils from a series of patients with severe sepsis and septic shock: (1) surface expression of receptors of the innate immunity; (2) production of inflammatory mediators and reactive oxygen species in response to bacterial agonists; (3) chemotaxis; (4) phagocytosis of Gram-positive and Gram-negative bacteria; and (5) ex vivo viability (life span) and resistance to apoptosis. Importantly, the investigators have developed and mastered all in vitro assays and cell separation techniques necessary to address and answer these important questions. This project will undoubtedly shed light on the fate and function of a prominent leukocyte population circulating in patients with severe bacterial infections and sepsis.

Conditions

Sepsis; SIRS

Keywords

Innate immunity; Neutrophils; Band forms

Outcome Measures

Primary Outcomes (1)

• Innate immune functions of neutrophils

  * Surface expression of receptors of the innate immunity in immature vs. mature neutrophils. * Production by immature vs. mature neutrophils of inflammatory mediators and reactive oxygen species in response to bacterial agonists. * Chemotaxis of immature vs. mature neutrophils. * Phagocytosis of Gram-positive and Gram-negative bacteria by immature vs. mature neutrophils. * Ex vivo viability and resistance to apoptosis of immature vs. mature neutrophils.

  12 months

Study Arms (3)

Sepsis patients

Patients presenting sepsis

SIRS patients

Patients presenting with the systemic inflammatory response syndrome

Healthy subjects

Healthy blood donors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

* Patients with severe sepsis or septic shock * Patients with a noninfectious systemic inflammatory response syndrome (SIRS) * Healthy donors

You may qualify if:

• Patients with severe sepsis or septic shock (according to ACCP/FCCM standard definitions) with \> 5% immature neutrophils.
• Patients with a noninfectious systemic inflammatory response syndrome (SIRS), e.g. patients with head trauma or multiple trauma with \> 5% immature neutrophils.
• Healthy donors

You may not qualify if:

• Severe immunosuppression (e.g. HIV with \< 200 CD4/mm3), treatment with glucocorticoids (\> 300 mg hydrocortisone/day) or other immunosuppressive therapy
• Neutropenia (neutrophils \< 0.5 G/l).
• Recent chemotherapy or administration of intravenous immunoglobulins within the last 4 weeks.

Sponsors & Collaborators

• University Hospital, Geneva: lead

Study Sites (1)

University Hospitals of Geneva, Intensive Care

Geneva, 1211, Switzerland

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

No samples retained

MeSH Terms

Conditions

Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Geneviève Drifte, MD

CONTACT

genevieve.drifte@unige.ch

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 1, 2010
• First Posted: July 2, 2010
• Study Start: May 1, 2010
• Primary Completion: August 1, 2011
• Study Completion: October 1, 2011
• Last Updated: July 2, 2010

Record last verified: 2010-02

Locations

CH (1)