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Deactivation of alveolar macrophages in septic neutropenic ARDS
Djamel Mokart1, Benoit P Guery, Reda Bouabdallah
1Department of Anesthesiology and Intensive Care Unit, Paoli-Calmette Institute, Marseille, France. mokartd@marseille.fnclcc.fr
Study Objectives:
Neutrophils often have been involved in the pathophysiology of ARDS. However, authentic ARDS has been described in patients with severe neutropenia, suggesting the presence of other potential mechanisms that are responsible of this syndrome. Alveolar macrophages (AMs) could be involved in the development of ARDS, and so we decided to study AM activation in neutropenic patients.
Patients:
We designed a prospective study and enrolled two subgroups of consecutive patients (group A, 18 patients; group B, 22 patients) with septic ARDS. In the first period, 7 of 18 patients were neutropenic, and in the second period 10 of 22 patients were neutropenic. All neutropenic patients were treated with granulocyte colony-stimulating factor (G-CSF).
Measurements And Results:
In group A, BAL fluid samples were analyzed for differential and total cell counts, and alveolar activation marker expression (ie, human leukocyte antigen [HLA]-DR locus) was determined. Basal and lipopolysaccharide (LPS)-stimulated production of tumor necrosis factor, interleukin (IL)-1 beta, IL-6, and IL-10 was evaluated in group B. In neutropenic patients, the BAL fluid total cell count and the neutrophil absolute count was significantly lower compared to those in nonneutropenic patients (p = 0.029 and p = 0.046, respectively). HLA-DR expression on AMs was significantly decreased (p = 0.016), and the percentage of AMs expressing HLA-DR was also significantly lower (p = 0.041). In neutropenic patients, the mean percentage of AMs expressing HLA-DR was significantly lower in deceased patients compared to survivors (30 +/- 7 vs 43 +/- 1, respectively; p = 0.047). Basal AMs released cytokines was comparable between the two groups; however, LPS stimulation yielded a deactivation of AMs in neutropenic patients.
Conclusion:
These results suggest a deactivation and/or hypoactivation of AMs in septic ARDS patients. This deactivation/hypoactivation could be linked to the use of G-CSF as this molecule has been shown to generate a down-regulation of HLA-DR expression.
Insights
Severe neutropenia in Acute Respiratory Distress Syndrome (ARDS) patients is linked to deactivated alveolar macrophages (AMs). This hypoactivation may be associated with granulocyte colony-stimulating factor (G-CSF) treatment, impacting immune responses in ARDS.
Area of Science:
- Immunology
- Critical Care Medicine
- Pulmonology
Background:
- Neutrophils are implicated in Acute Respiratory Distress Syndrome (ARDS) pathophysiology.
- ARDS has been observed in neutropenic patients, suggesting alternative mechanisms.
- Alveolar macrophages (AMs) are potential key players in ARDS development.
Purpose of the Study:
- To investigate AM activation in neutropenic patients with septic ARDS.
- To compare AM activation markers between neutropenic and non-neutropenic ARDS patients.
Main Methods:
- Prospective study design enrolling patients with septic ARDS.
- Analysis of bronchoalveolar lavage (BAL) fluid for cell counts and human leukocyte antigen (HLA)-DR expression on AMs.
- Evaluation of cytokine production (TNF, IL-1β, IL-6, IL-10) in response to lipopolysaccharide (LPS) stimulation.
Main Results:
- Neutropenic patients had significantly lower BAL fluid total and neutrophil counts.
- Decreased expression of HLA-DR on AMs was observed in neutropenic patients.
- AMs from neutropenic patients showed hypoactivation upon LPS stimulation, with lower HLA-DR expression in non-survivors.
Conclusions:
- Alveolar macrophages (AMs) exhibit deactivation or hypoactivation in septic ARDS patients with neutropenia.
- Granulocyte colony-stimulating factor (G-CSF) treatment may contribute to AM hypoactivation by down-regulating HLA-DR expression.
- These findings highlight the role of AMs in ARDS pathophysiology, particularly in the context of neutropenia and G-CSF therapy.