Alveolar macrophages in idiopathic pulmonary fibrosis have glucocorticoid receptors, but glucocorticoid therapy does not suppress alveolar macrophage release of fibronectin and alveolar macrophage derived growth factor

J. G. Lacronique, S. I. Rennard, P. B. Bitterman, T. Ozaki, Ronald Crystal

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Abstract

Although glucocorticoids are the most widely used therapeutic modality in the treatment of idiopathic pulmonary fibrosis (IPF), the administration of these agents infrequently arrests the progressive fibrosis of this disorder. In this context, the present study was designed to determine if the lack of effect of glucocorticoid therapy in IPF could be explained, in part, by a lack of effect of glucocorticoids on alveolar macrophage release of fibronectin and alveolar macrophage derived growth factor (AMDGF), mediators thought to play a role in the accumulation of fibroblasts associated with the fibrosis of this disease. Patients with IPF were studied in 2 groups, those receiving glucocorticoid therapy and those not receiving therapy. The release of fibronectin by alveolar macrophages of IPF patients was elevated compared to release of fibronectin from alveolar macrophages obtained from normal volunteers (p < 0.01). However, the release of fibronectin was no different in treated and untreated patients with IPF (p > 0.2). Like fibronectin, the release of AMDGF by alveolar macrophages of IPF patients was elevated compared to release of AMDGF from alveolar macrophages obtained from normal volunteers (p < 0.01), but there was no difference in treated and untreated IPF patients (p > 0.2). Sequential evaluation of IPF patients before and after glucocorticoid therapy demonstrated no impact of glucocorticoid therapy on alveolar macrophage release of fibronectin and AMDGF. The inability of glucocorticoids to suppress fibronectin and AMDGF release was not due to a lack of glucocorticoid receptors in IPF patients because alveolar macrophages from patients and from normal volunteers bound glucocorticoids similarly. Moreover, although in vitro incubation of macrophages from patients with IPF with glucocorticoids could not suppress fibronectin or AMDGF release, alveolar macrophage production of PGE2 was suppressed, demonstrating that the glucocorticoid receptors of alveolar macrophages of patients with IPF were functional. The inability of glucocorticoids to suppress alveolar macrophage release of fibronectin and AMDGF, 2 mediators thought to modulate the recruitment and replication of fibroblasts within the pulmonary parenchyma, may account, at least in part, for the limited therapeutic benefit obtained with glucocorticoid therapy in this disorder.

Original languageEnglish
Pages (from-to)450-456
Number of pages7
JournalAmerican Review of Respiratory Disease
Volume130
Issue number3
Publication statusPublished - 1 Nov 1984
Externally publishedYes

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Idiopathic Pulmonary Fibrosis
Glucocorticoid Receptors
Alveolar Macrophages
Fibronectins
Glucocorticoids
Therapeutics
Healthy Volunteers
Fibrosis
alveolar macrophage growth factor
Fibroblasts
Dinoprostone
Macrophages

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

@article{b6238c1a181b4bc28c887676c0a0e4c6,
title = "Alveolar macrophages in idiopathic pulmonary fibrosis have glucocorticoid receptors, but glucocorticoid therapy does not suppress alveolar macrophage release of fibronectin and alveolar macrophage derived growth factor",
abstract = "Although glucocorticoids are the most widely used therapeutic modality in the treatment of idiopathic pulmonary fibrosis (IPF), the administration of these agents infrequently arrests the progressive fibrosis of this disorder. In this context, the present study was designed to determine if the lack of effect of glucocorticoid therapy in IPF could be explained, in part, by a lack of effect of glucocorticoids on alveolar macrophage release of fibronectin and alveolar macrophage derived growth factor (AMDGF), mediators thought to play a role in the accumulation of fibroblasts associated with the fibrosis of this disease. Patients with IPF were studied in 2 groups, those receiving glucocorticoid therapy and those not receiving therapy. The release of fibronectin by alveolar macrophages of IPF patients was elevated compared to release of fibronectin from alveolar macrophages obtained from normal volunteers (p < 0.01). However, the release of fibronectin was no different in treated and untreated patients with IPF (p > 0.2). Like fibronectin, the release of AMDGF by alveolar macrophages of IPF patients was elevated compared to release of AMDGF from alveolar macrophages obtained from normal volunteers (p < 0.01), but there was no difference in treated and untreated IPF patients (p > 0.2). Sequential evaluation of IPF patients before and after glucocorticoid therapy demonstrated no impact of glucocorticoid therapy on alveolar macrophage release of fibronectin and AMDGF. The inability of glucocorticoids to suppress fibronectin and AMDGF release was not due to a lack of glucocorticoid receptors in IPF patients because alveolar macrophages from patients and from normal volunteers bound glucocorticoids similarly. Moreover, although in vitro incubation of macrophages from patients with IPF with glucocorticoids could not suppress fibronectin or AMDGF release, alveolar macrophage production of PGE2 was suppressed, demonstrating that the glucocorticoid receptors of alveolar macrophages of patients with IPF were functional. The inability of glucocorticoids to suppress alveolar macrophage release of fibronectin and AMDGF, 2 mediators thought to modulate the recruitment and replication of fibroblasts within the pulmonary parenchyma, may account, at least in part, for the limited therapeutic benefit obtained with glucocorticoid therapy in this disorder.",
author = "Lacronique, {J. G.} and Rennard, {S. I.} and Bitterman, {P. B.} and T. Ozaki and Ronald Crystal",
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T1 - Alveolar macrophages in idiopathic pulmonary fibrosis have glucocorticoid receptors, but glucocorticoid therapy does not suppress alveolar macrophage release of fibronectin and alveolar macrophage derived growth factor

AU - Lacronique, J. G.

AU - Rennard, S. I.

AU - Bitterman, P. B.

AU - Ozaki, T.

AU - Crystal, Ronald

PY - 1984/11/1

Y1 - 1984/11/1

N2 - Although glucocorticoids are the most widely used therapeutic modality in the treatment of idiopathic pulmonary fibrosis (IPF), the administration of these agents infrequently arrests the progressive fibrosis of this disorder. In this context, the present study was designed to determine if the lack of effect of glucocorticoid therapy in IPF could be explained, in part, by a lack of effect of glucocorticoids on alveolar macrophage release of fibronectin and alveolar macrophage derived growth factor (AMDGF), mediators thought to play a role in the accumulation of fibroblasts associated with the fibrosis of this disease. Patients with IPF were studied in 2 groups, those receiving glucocorticoid therapy and those not receiving therapy. The release of fibronectin by alveolar macrophages of IPF patients was elevated compared to release of fibronectin from alveolar macrophages obtained from normal volunteers (p < 0.01). However, the release of fibronectin was no different in treated and untreated patients with IPF (p > 0.2). Like fibronectin, the release of AMDGF by alveolar macrophages of IPF patients was elevated compared to release of AMDGF from alveolar macrophages obtained from normal volunteers (p < 0.01), but there was no difference in treated and untreated IPF patients (p > 0.2). Sequential evaluation of IPF patients before and after glucocorticoid therapy demonstrated no impact of glucocorticoid therapy on alveolar macrophage release of fibronectin and AMDGF. The inability of glucocorticoids to suppress fibronectin and AMDGF release was not due to a lack of glucocorticoid receptors in IPF patients because alveolar macrophages from patients and from normal volunteers bound glucocorticoids similarly. Moreover, although in vitro incubation of macrophages from patients with IPF with glucocorticoids could not suppress fibronectin or AMDGF release, alveolar macrophage production of PGE2 was suppressed, demonstrating that the glucocorticoid receptors of alveolar macrophages of patients with IPF were functional. The inability of glucocorticoids to suppress alveolar macrophage release of fibronectin and AMDGF, 2 mediators thought to modulate the recruitment and replication of fibroblasts within the pulmonary parenchyma, may account, at least in part, for the limited therapeutic benefit obtained with glucocorticoid therapy in this disorder.

AB - Although glucocorticoids are the most widely used therapeutic modality in the treatment of idiopathic pulmonary fibrosis (IPF), the administration of these agents infrequently arrests the progressive fibrosis of this disorder. In this context, the present study was designed to determine if the lack of effect of glucocorticoid therapy in IPF could be explained, in part, by a lack of effect of glucocorticoids on alveolar macrophage release of fibronectin and alveolar macrophage derived growth factor (AMDGF), mediators thought to play a role in the accumulation of fibroblasts associated with the fibrosis of this disease. Patients with IPF were studied in 2 groups, those receiving glucocorticoid therapy and those not receiving therapy. The release of fibronectin by alveolar macrophages of IPF patients was elevated compared to release of fibronectin from alveolar macrophages obtained from normal volunteers (p < 0.01). However, the release of fibronectin was no different in treated and untreated patients with IPF (p > 0.2). Like fibronectin, the release of AMDGF by alveolar macrophages of IPF patients was elevated compared to release of AMDGF from alveolar macrophages obtained from normal volunteers (p < 0.01), but there was no difference in treated and untreated IPF patients (p > 0.2). Sequential evaluation of IPF patients before and after glucocorticoid therapy demonstrated no impact of glucocorticoid therapy on alveolar macrophage release of fibronectin and AMDGF. The inability of glucocorticoids to suppress fibronectin and AMDGF release was not due to a lack of glucocorticoid receptors in IPF patients because alveolar macrophages from patients and from normal volunteers bound glucocorticoids similarly. Moreover, although in vitro incubation of macrophages from patients with IPF with glucocorticoids could not suppress fibronectin or AMDGF release, alveolar macrophage production of PGE2 was suppressed, demonstrating that the glucocorticoid receptors of alveolar macrophages of patients with IPF were functional. The inability of glucocorticoids to suppress alveolar macrophage release of fibronectin and AMDGF, 2 mediators thought to modulate the recruitment and replication of fibroblasts within the pulmonary parenchyma, may account, at least in part, for the limited therapeutic benefit obtained with glucocorticoid therapy in this disorder.

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