Limits...
Macrophage activation in acute exacerbation of idiopathic pulmonary fibrosis.

Schupp JC, Binder H, Jäger B, Cillis G, Zissel G, Müller-Quernheim J, Prasse A - PLoS ONE (2015)

Bottom Line: In patients with AE, the percentage of BAL neutrophils was significantly increased compared to stable patients.We found an increase in the production rate of the pro-inflammatory cytokines CXCL1 and IL-8 combined with an increase in all tested M2 cytokines by BAL-cells.Furthermore, high baseline levels of CCL18 production by BAL cells were significantly predictive for the development of future AE.

View Article: PubMed Central - PubMed

Affiliation: Department of Pneumology, University Medical Centre, Freiburg, Germany.

ABSTRACT

Background: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is a common cause of disease acceleration in IPF and has a major impact on mortality. The role of macrophage activation in AE of IPF has never been addressed before.

Methods: We evaluated BAL cell cytokine profiles and BAL differential cell counts in 71 IPF patients w/wo AE and in 20 healthy volunteers. Twelve patients suffered from AE at initial diagnosis while sixteen patients developed AE in the 24 months of follow-up. The levels of IL-1ra, CCL2, CCL17, CCL18, CCL22, TNF-α, IL-1β, CXCL1 and IL-8 spontaneously produced by BAL-cells were analysed by ELISA.

Results: In patients with AE, the percentage of BAL neutrophils was significantly increased compared to stable patients. We found an increase in the production rate of the pro-inflammatory cytokines CXCL1 and IL-8 combined with an increase in all tested M2 cytokines by BAL-cells. An increase in CCL18 levels and neutrophil counts during AE was observed in BAL cells from patients from whom serial lavages were obtained. Furthermore, high baseline levels of CCL18 production by BAL cells were significantly predictive for the development of future AE.

Conclusions: BAL cell cytokine production levels at acute exacerbation show up-regulation of pro-inflammatory as well as anti-inflammatory/ M2 cytokines. Our data suggest that AE in IPF is not an incidental event but rather driven by cellular mechanisms including M2 macrophage activation.

Show MeSH

Related in: MedlinePlus

Course of spontaneous production of CCL18 and neutrophil cell count before and during an AE.A: Course of spontaneous production of CCL18 protein by BAL cells and B: Percentage of neutrophile granulocytes of BAL of seven patients with IPF before (preAE) and during an AE (AE). Each color represents a distinct patient. (* p<0.05).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4295887&req=5

pone.0116775.g002: Course of spontaneous production of CCL18 and neutrophil cell count before and during an AE.A: Course of spontaneous production of CCL18 protein by BAL cells and B: Percentage of neutrophile granulocytes of BAL of seven patients with IPF before (preAE) and during an AE (AE). Each color represents a distinct patient. (* p<0.05).

Mentions: From seven patients with IPF we obtained BAL at baseline and during AE at a later time point. The spontaneous chemokine production at initial diagnosis and during the acute exacerbation was measured (Fig. 2). CCL18 production was significantly increased (p = 0.04) during acute exacerbation. CCL18 was elevated despite a non-significant decrease of alveolar macrophages from 79.8% to 69.8% on average and a significant increase of neutrophils from 5.8% to 18.0% on average (p = 0.04) during acute exacerbation in these patients. There was a non-significant trend towards increased levels of the M2 chemokines CCL17, CCL22, and IL-1β during AE (data not shown).


Macrophage activation in acute exacerbation of idiopathic pulmonary fibrosis.

Schupp JC, Binder H, Jäger B, Cillis G, Zissel G, Müller-Quernheim J, Prasse A - PLoS ONE (2015)

Course of spontaneous production of CCL18 and neutrophil cell count before and during an AE.A: Course of spontaneous production of CCL18 protein by BAL cells and B: Percentage of neutrophile granulocytes of BAL of seven patients with IPF before (preAE) and during an AE (AE). Each color represents a distinct patient. (* p<0.05).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4295887&req=5

pone.0116775.g002: Course of spontaneous production of CCL18 and neutrophil cell count before and during an AE.A: Course of spontaneous production of CCL18 protein by BAL cells and B: Percentage of neutrophile granulocytes of BAL of seven patients with IPF before (preAE) and during an AE (AE). Each color represents a distinct patient. (* p<0.05).
Mentions: From seven patients with IPF we obtained BAL at baseline and during AE at a later time point. The spontaneous chemokine production at initial diagnosis and during the acute exacerbation was measured (Fig. 2). CCL18 production was significantly increased (p = 0.04) during acute exacerbation. CCL18 was elevated despite a non-significant decrease of alveolar macrophages from 79.8% to 69.8% on average and a significant increase of neutrophils from 5.8% to 18.0% on average (p = 0.04) during acute exacerbation in these patients. There was a non-significant trend towards increased levels of the M2 chemokines CCL17, CCL22, and IL-1β during AE (data not shown).

Bottom Line: In patients with AE, the percentage of BAL neutrophils was significantly increased compared to stable patients.We found an increase in the production rate of the pro-inflammatory cytokines CXCL1 and IL-8 combined with an increase in all tested M2 cytokines by BAL-cells.Furthermore, high baseline levels of CCL18 production by BAL cells were significantly predictive for the development of future AE.

View Article: PubMed Central - PubMed

Affiliation: Department of Pneumology, University Medical Centre, Freiburg, Germany.

ABSTRACT

Background: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is a common cause of disease acceleration in IPF and has a major impact on mortality. The role of macrophage activation in AE of IPF has never been addressed before.

Methods: We evaluated BAL cell cytokine profiles and BAL differential cell counts in 71 IPF patients w/wo AE and in 20 healthy volunteers. Twelve patients suffered from AE at initial diagnosis while sixteen patients developed AE in the 24 months of follow-up. The levels of IL-1ra, CCL2, CCL17, CCL18, CCL22, TNF-α, IL-1β, CXCL1 and IL-8 spontaneously produced by BAL-cells were analysed by ELISA.

Results: In patients with AE, the percentage of BAL neutrophils was significantly increased compared to stable patients. We found an increase in the production rate of the pro-inflammatory cytokines CXCL1 and IL-8 combined with an increase in all tested M2 cytokines by BAL-cells. An increase in CCL18 levels and neutrophil counts during AE was observed in BAL cells from patients from whom serial lavages were obtained. Furthermore, high baseline levels of CCL18 production by BAL cells were significantly predictive for the development of future AE.

Conclusions: BAL cell cytokine production levels at acute exacerbation show up-regulation of pro-inflammatory as well as anti-inflammatory/ M2 cytokines. Our data suggest that AE in IPF is not an incidental event but rather driven by cellular mechanisms including M2 macrophage activation.

Show MeSH
Related in: MedlinePlus