0
Original Research: ASTHMA |

The Effects of Smoking on the Lipopolysaccharide Response and Glucocorticoid Sensitivity of Alveolar Macrophages of Patients With Asthma

Binita Kane, MBChB; Umme Kolsum, MPhil; Thomas Southworth, PhD; Jane Armstrong, BSc; Ashley Woodcock, MD; Dave Singh, MD
Author and Funding Information

From the School of Translational Medicine, University of Manchester, University Hospital of South Manchester Foundation Trust, Manchester, UK.

Correspondence to: Binita Kane, MBChB, University of Manchester, Medicines Evaluation Unit, Wythenshawe Hospital, Manchester M23 9QZ, UK; e-mail: binitakane@yahoo.com


All work for this study was carried out in the University Hospital of South Manchester Foundation Trust, with the exception of polymerase chain reaction work, which was conducted at AstraZeneca Pharmaceuticals (Charnwood, UK).

This study was partly funded by an unrestricted grant from AstraZeneca.

Dr. Singh has received lecture fees, research grants, consultancy fees, and support for conference attendance from a number of pharmaceutical companies, including AstraZeneca, GlaxoSmithKline, Chiesi, Boehringer Ingelheim, and Roche. Drs. Kane, Southworth, and Woodcock, Ms. Kolsum, and Ms. Armstrong have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).


© 2009 American College of Chest Physicians


Chest. 2009;136(1):163-170. doi:10.1378/chest.08-2633
Text Size: A A A
Published online

Background:  Cigarette smoking in asthma patients causes insensitivity to inhaled glucocorticoids (GCs). We tested the hypothesis that smoking causes GC insensitivity in alveolar macrophages (AMs) obtained from patients with asthma.

Methods:  Nineteen asthmatic nonsmokers (ANSs) and 13 asthmatic smokers (ASMs) underwent BAL. AMs were cultured with or without dexamethasone, 0.1 to 1,000 nmol/L, for 2 h before lipopolysaccharide (LPS) [1 μg/mL] stimulation. After 6 h, supernatants were harvested for enzyme-linked immunosorbent assay, and messenger RNA was collected for real-time (RT)-polymerase chain reaction (PCR).

Results:  ASMs had higher numbers of AMs per milliliter of BAL fluid than ANSs (1.98 vs 0.75 × 106 cells/mL, respectively; p = 0.007). Cigarette smoking significantly attenuated the LPS response for all three cytokines tested among ANSs vs ASMs (tumor necrosis factor [TNF]-α, 31.6 vs 10.6 ng/mL, respectively (p = 0.01); interleukin [IL]-6, 25.8 vs 10.8 ng/mL, respectively (p = 0.002); IL-8, 62.5 vs 36.1 ng/mL, respectively (p = 0.001)). There was no difference in dexamethasone dose-response curves between ANSs and ASMs (p > 0.05 for all comparisons). The inhibitory concentration of 50% (IC50) for IL-6 was 120.6 vs 83.3, respectively, and for TNF-α it was 4.9 vs 8.6, respectively; an IC50 was not achieved for IL-8. RT-PCR also showed no difference in the suppression of cytokine messenger RNA levels between groups, with IL-8 being the most GC-insensitive cytokine.

Conclusion:  Cigarette smoking in patients with asthma increases the number of airway AMs and attenuates their response to LPS, which may have implications in host immune function. Cigarette smoking does not alter the GC sensitivity of AMs in patients with asthma. There was differential cytokine sensitivity, with IL-8 being the least GC-sensitive cytokine. GC-insensitive IL-8 production from AMs may be a mechanism by which neutrophils are attracted into the airways.

Figures in this Article

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543