Clinical trial NCT03231670: Innate Immune Response of Blood Cells in Patients With Pneumonia
Official title: Analysis of Blood Cells Innate Immune Response in Patients With Lobar Pneumonia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Lobar Pneumonia
Lead sponsor: Lille Catholic University
Sponsor class: OTHER
Collaborators: name: Institut Pasteur de Lille
First posted: 2017-07-27
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patient hospitalized in the department of pneumology for whom clinical, radiological and biological criteria confirm the diagnosis of lobar pneumonia

Brief summary: Pulmonary bacterial infections such as exacerbations of chronic bronchitis, nosocomial and community-acquired pneumonia represent a major public health issue. Antibiotics have shown their efficacy by direct antimicrobial activity and their limit particularly in case of multidrug-resistant microorganisms or in treating patients with aggravating pathologies. Innate immunity could be an alternative or complementary therapeutic pathway. Innate immunity receptors bind universal and invariant microbial molecular patterns present in bacteria, virus, fungus or parasite. Toll-like Receptors (TLR) activation by microbial agonist stimulates the innate immunity response which results in the production of chemokines, cytokines, antimicrobial molecules and the recruitment of innate cells.

The " Pulmonary Infection and Innate Immunity " team of the Immunity and Infection Center in Lille (Group of Dr. Sirard and Carnoy) has a long expertise in the study of TLR5 and its agonist, the flagellin, a structural protein of bacterial flagella. TLR5 is expressed on the cell surface of macrophages, monocytes, dendritic and epithelial cells. Several studies in mice have shown the flagellin prophylactic potential during bacterial infections through a TLR5 dependent stimulation of innate immunity. Recently, the group of Dr. Sirard and Carnoy has shown that flagellin can be used in association with antibiotics to treat Streptococcus pneumoniae respiratory infections in mice. The results demonstrate that an agonist of TLR can increase the therapeutic index of an antibiotic and improve the pulmonary anti-infectious reaction. This innovative approach allows us to consider new antibacterial strategies where antibiotics have reached their limit (nosocomial infection, multidrug-resistant bacteria...). TLR agonists can activate multiple human cell type. Indeed, blood cells activation by TLR agonists have been recently characterized in healthy volunteers.

However, there is no available data on the ability of TLR agonists to activate cells from patients with infectious pneumopathies. A study in these patients is inevitable if one is to consider the therapeutic use of agonists in respiratory pathologies.


Eligibility criteria: Inclusion Criteria:

* Adult patient hospitalized in the department of pneumology for whom clinical, radiological and biological criteria confirm the diagnosis of lobar pneumonia
* Beneficiary of the French National Health Insurance Fund
* Signed informed consent form

Exclusion Criteria:

* Patient under guardianship
* Patient with acute respiratory distress syndrome or septic shock
* Pregnant women
* Patient with HIV, HCV or Mycobacterium tuberculosis
* Transplanted patient receiving immunosuppressive therapy

Primary outcomes:
measure: Change in IL-6 specific transcripts
timeFrame: Baseline and 2 months
Secondary outcomes:
measure: Change in expression of innate immunity genes after stimulation by TLR2 agonist
timeFrame: Baseline and 2 months
measure: Change in expression of innate immunity genes after stimulation by TLR4 agonist
timeFrame: Baseline and 2 months
measure: Change in expression of innate immunity genes after stimulation by TLR5 agonist
timeFrame: Baseline and 2 months
measure: Change in expression of innate immunity genes after stimulation by TLR9 agonist
timeFrame: Baseline and 2 months
measure: Change in ELISA assay on mediators of inflammation with stimulation by TRL2 agonist
timeFrame: Baseline and 2 months
measure: Change in ELISA assay on mediators of inflammation with stimulation by TRL4 agonist
timeFrame: Baseline and 2 months
measure: Change in ELISA assay on mediators of inflammation with stimulation by TRL5 agonist
timeFrame: Baseline and 2 months
measure: Change in ELISA assay on mediators of inflammation with stimulation by TRL9 agonist
timeFrame: Baseline and 2 months
measure: Genotyping of TLR 2 gene
timeFrame: Baseline
measure: Genotyping of TLR 4 gene
timeFrame: Baseline
measure: Genotyping of TLR 5 gene
timeFrame: Baseline
measure: Genotyping of TLR 9 gene
timeFrame: Baseline
Other outcomes:
Locations:
city: Lomme
country: France
facility: Hôpital Saint-Philibert
state: Hauts De France
Study officials:
affiliation: Institut Pasteur de Lille
name: Christophe Carnoy, PhD
role: STUDY_DIRECTOR
affiliation: Institut Pasteur de Lille
name: Jean-Claude Sirard, PhD
role: STUDY_DIRECTOR
References: