PMID- 12907555 OWN - NLM STAT- MEDLINE DCOM- 20030904 LR - 20201208 IS - 0012-3692 (Print) IS - 0012-3692 (Linking) VI - 124 IP - 2 DP - 2003 Aug TI - Deactivation of alveolar macrophages in septic neutropenic ARDS. PG - 644-52 AB - 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. FAU - Mokart, Djamel AU - Mokart D AD - Department of Anesthesiology and Intensive Care Unit, Paoli-Calmette Institute, Marseille, France. mokartd@marseille.fnclcc.fr FAU - Guery, Benoit P AU - Guery BP FAU - Bouabdallah, Reda AU - Bouabdallah R FAU - Martin, Claude AU - Martin C FAU - Blache, Jean-Louis AU - Blache JL FAU - Arnoulet, Christine AU - Arnoulet C FAU - Mege, Jean-Louis AU - Mege JL LA - eng PT - Journal Article PL - United States TA - Chest JT - Chest JID - 0231335 RN - 0 (Cytokines) RN - 0 (HLA-DR Antigens) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) SB - IM MH - Adult MH - Aged MH - Cytokines/biosynthesis MH - Female MH - Granulocyte Colony-Stimulating Factor/therapeutic use MH - HLA-DR Antigens/*metabolism MH - Humans MH - Macrophage Activation MH - Macrophages, Alveolar/*metabolism MH - Male MH - Middle Aged MH - *Neutropenia/complications/drug therapy/mortality MH - Prognosis MH - Prospective Studies MH - *Respiratory Distress Syndrome/complications/mortality/physiopathology EDAT- 2003/08/09 05:00 MHDA- 2003/09/05 05:00 CRDT- 2003/08/09 05:00 PHST- 2003/08/09 05:00 [pubmed] PHST- 2003/09/05 05:00 [medline] PHST- 2003/08/09 05:00 [entrez] AID - S0012-3692(15)33351-1 [pii] AID - 10.1378/chest.124.2.644 [doi] PST - ppublish SO - Chest. 2003 Aug;124(2):644-52. doi: 10.1378/chest.124.2.644.