Neutrophil Apoptosis, Activation and Anti-Inflammatory Cytokine Response in Granulocyte Colony-Stimulating Factor-Treated Patients with Community-Acquired Pneumonia

Abstract

Background:Despite antibiotic treatment, the mortality of severe community-acquired pneumonia (CAP), especially in patients with severe comorbidity, remains high. Innate defense mechanisms including polymorphonuclear neutrophil (PMN) activation and survival, orchestrated by cytokines, are primarily responsible for the elimination of bacterial organisms from the alveolus. Objectives: The aim of this study was to evaluate the effect of granulocyte colony-stimulating factor (G-CSF) on PMN activation, apoptosis and cytokine response in patients with CAP. Methods: Patients received a single dose of G-CSF (1 × 300 or 480 µg s.c.) prior to standard antibiotic treatment (n = 8) or standard treatment only (n = 8). Apoptosis rate and expression of CD11b, CD66b, CD64 and CD114 surface molecules on systemic PMN were assessedusing fluorescence-activated cell sorter analysis. Levels of the interleukin-1 receptor antagonist (IL-1RA), the soluble tumor necrosis factor receptor inhibitor (sTNF-p55) and G-CSF were measured by ELISA. Results: In the treatment group, 12 h after G-CSF application, neutrophil count increased, neutrophil activation marker CD11b was stimulated (CD11b: 48.6 ± 9.7 vs. 71.2 ± 17.7, p < 0.01), neutrophil apoptosis decreased (apoptosis: 1.36 ± 0.27 vs. 0.2 ± 0.12%, p < 0.01) and the concentration of IL-1RA and sTNF-p55 increased (IL-1RA 136.4 ± 72.2 vs. 340.1 ± 194.6 ng/ml, p < 0.01; sTNF-p55 382 ± 4,243 vs. 632 ± 4,714 ng/ml, p < 0.01; control group nonsignificant). These effects were not seen in the control group. Conclusions: The application of a single dose of G-CSF in patients with CAP caused a prolonged survival and increased activation of neutrophils combined with a sustained release of anti-inflammatory cytokines.

Surfactant Proteins A and D Suppress Alveolar Macrophage Phagocytosis via Interaction with SIRPα

“…Massive numbers of neutrophils migrate to the airspaces in community-acquired pneumonia and the acute respiratory distress syndrome (ARDS), yet the burden of apoptotic cells is surprisingly low (37)(38)(39). We therefore questioned if the tonic suppression displayed by resting AMs could be overcome during acute inflammation.…”

Resolution of neutrophilic inflammation by H2O2 in antigen‐induced arthritis

“…Accumulation of a particular leukocyte subset in tissue depends not only on the number of cells being recruited, but also on the number of cells that are cleared (by apoptosis) or leave the tissue (9). Recent studies have shown that apoptosis of neutrophils contributes to natural or induced (by antiinflammatory agents) resolution of inflammation (10, 11).…”

Community‐acquired lobar pneumonia caused by Pseudomonas aeruginosa infection in Japan: A case report with histological and immunohistochemical examination

“…Accumulation of macrophages in the affected alveoli is a general finding of lobar pneumonia. Bacterial infection initiates an acute inflammatory response characterized by rapid recruitment of macrophages and neutrophils and release proinflammatory cytokines including tumor necrosis factor–α and interleukinin–1 . These proinflammatory cytokines are necessary for local bacterial defense and clearance, but systemic overproduction of proinflammatory cytokines is thought to be a central factor in uncontrolled sepsis and septic shock.…”