Characterization of Non-canonical Way in Inflammasome Monocytes of Patients With Severe Sepsis

NCT02539147 | Completed

• 1 other identifier: 2013-A01617-38
• Study Type: observational
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Activation of caspase-4 and human caspase-5 (orthologs of caspase-11 in mice) in innate immune cells.

Conditions

Severe Sepsis

Keywords

lipopolysaccharide; sepsis; caspase-4 and -5; monocytes; IL-1β and IL-1α

Outcome Measures

Primary Outcomes (1)

• Characterize the expression of caspase-4 and -5 in by measuring the production of cytokines: IL-1β concentrations and IL-1α will determined by ELISA in the cell supernatant will be collected from monocytes stimulated or not

  Two hours after blood collection : isolation and stimulation of monocytes than preparation of cell lysates

Secondary Outcomes (1)

• Correlate the activation of caspases-4 and -5 with IL-1β production with (canonical inflammasome) and IL-1α (Non-canonical inflammasome) measured by Western blot

  Two hours after blood collection : isolation and stimulation of monocytes than preparation of cell lysates

Study Arms (1)

patients with severe sepsis

blood samples from patients with severe sepsis

Biological: blood samples

Interventions

blood samples BIOLOGICAL

Isolation and stimulation of monocytes, preparation of cell lysates, measurement of cytokine production, Western blot

patients with severe sepsis

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with sepsis severe (bacterial infection associated with deterioration of at least one vital function) defined according to the criteria consensus conference

You may qualify if:

• patients with sepsis severe (bacterial infection associated with deterioration of at least one vital function) defined according to the criteria consensus conference
• patients whose diagnosis is made within 24 hours of the opening hours of Pasteur Research Laboratory
• patients with arterial catheter (not to impose an additional puncture to the patient) will be recruited in the intensive care unit of the Hospital St. Joseph. Arterial blood (20 ml) will be charged within 24 hours of the onset of severe sepsis criteria, during working hours of the laboratory of the Pasteur Institute, using vacuum tubes under heparin (Vacutainer), sent by a courier within 2 hours following the removal (to ensure that the cells are sufficiently "fresh" during processing in the laboratory)

You may not qualify if:

• none

Sponsors & Collaborators

• Fondation Hôpital Saint-Joseph: lead
• Institut Pasteur: collaborator
• Agency for Science, Technology and Research: collaborator

Study Sites (1)

Groupe Hospitalier Paris Saint Joseph

Paris, Île-de-France Region, 75014, France

Location

Related Publications (5)

• Conforti-Andreoni C, Ricciardi-Castagnoli P, Mortellaro A. The inflammasomes in health and disease: from genetics to molecular mechanisms of autoinflammation and beyond. Cell Mol Immunol. 2011 Mar;8(2):135-45. doi: 10.1038/cmi.2010.81. Epub 2011 Jan 24.

  PMID: 21258359 BACKGROUND

• Zambetti LP, Laudisi F, Licandro G, Ricciardi-Castagnoli P, Mortellaro A. The rhapsody of NLRPs: master players of inflammation...and a lot more. Immunol Res. 2012 Sep;53(1-3):78-90. doi: 10.1007/s12026-012-8272-z.

  PMID: 22427013 BACKGROUND

• Vigano E, Mortellaro A. Caspase-11: the driving factor for noncanonical inflammasomes. Eur J Immunol. 2013 Sep;43(9):2240-5. doi: 10.1002/eji.201343800.

  PMID: 24037676 BACKGROUND

• Kayagaki N, Warming S, Lamkanfi M, Vande Walle L, Louie S, Dong J, Newton K, Qu Y, Liu J, Heldens S, Zhang J, Lee WP, Roose-Girma M, Dixit VM. Non-canonical inflammasome activation targets caspase-11. Nature. 2011 Oct 16;479(7371):117-21. doi: 10.1038/nature10558.

  PMID: 22002608 BACKGROUND

• Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992 Jun;101(6):1644-55. doi: 10.1378/chest.101.6.1644.

  PMID: 1303622 BACKGROUND

Biospecimen

Retention: NONE RETAINED

arterial blood (20ml)

MeSH Terms

Conditions

Sepsis

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Benoit Misset, Professor

  Fondation Hôpital Saint-Joseph

  PRINCIPAL INVESTIGATOR

• Jean Marc Cavaillon, Professor

  Unité Cytokines et Inflammation, Institut Pasteur, Paris

  PRINCIPAL INVESTIGATOR

• Alessandra Mortellaro

  Singapore Immunology Network, Agency for Science, Technology and Research, 8A Biomedical Grove, #04-06 Immunos, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2015
• First Posted: September 2, 2015
• Study Start: September 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: February 23, 2017

Record last verified: 2015-08

Locations

FR (1)