Bacteria Challenge in Smoke-exposed Mice Exacerbates Inflammation and Skews the Inflammatory Profile

The pathogenesis of chronic obstructive pulmonary disease is associated with acute episodes of bacterial exacerbations. The most commonly isolated bacteria during episodes of exacerbation is nontypeable Haemophilus influenzae (NTHI). In this study, we investigated the in vivo consequences of cigaret...

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Bibliographic Details
Published in:American journal of respiratory and critical care medicine Vol. 179; no. 8; pp. 666 - 675
Main Authors: Gaschler, Gordon J, Skrtic, Marko, Zavitz, Caleb C. J, Lindahl, Maria, Onnervik, Per-Ola, Murphy, Timothy F, Sethi, Sanjay, Stampfli, Martin R
Format: Journal Article
Language:English
Published: New York, NY Am Thoracic Soc 15.04.2009
American Thoracic Society
Subjects:
Administration, Intranasal
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Bacteria
Bacterial infections
Biological and medical sciences
Chronic obstructive pulmonary disease
Cigarettes
Disease Progression
Emergency and intensive care: infection, septic shock
Female
Haemophilus influenzae
Haemophilus influenzae - immunology
Inflammation
Inflammation - etiology
Inflammation - microbiology
Intensive care medicine
Lungs
Medical sciences
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Pathogenesis
Pulmonary Disease, Chronic Obstructive - immunology
Pulmonary Disease, Chronic Obstructive - microbiology
Smoking
Steroids
Tobacco Smoke Pollution - adverse effects
Tumor necrosis factor-TNF
Canada
Lung disease
Intensive care
mouse model
Respiratory disease
Rodentia
Inflammation
Haemophilus influenzae
exacerbation
Pasteurellaceae
Vertebrata
Mammalia
Mouse
Animal
nontypeable Haemophilus influenzae
Bacteria
Bronchus disease
Chronic obstructive pulmonary disease
Resuscitation
ISSN:1073-449X, 1535-4970, 1535-4970
Online Access:Get full text
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Summary:The pathogenesis of chronic obstructive pulmonary disease is associated with acute episodes of bacterial exacerbations. The most commonly isolated bacteria during episodes of exacerbation is nontypeable Haemophilus influenzae (NTHI). In this study, we investigated the in vivo consequences of cigarette smoke exposure on the inflammatory response to an NTHI challenge. C57BL/6 and BALB/c mice were exposed to cigarette smoke for 8 weeks and subsequently challenged intranasally with NTHI. We observed increased pulmonary inflammation and lung damage in cigarette smoke-exposed NTHI-challenged mice as compared with control NTHI-challenged mice. Furthermore, although NTHI challenge in control mice was marked by increases in tumor necrosis factor-alpha, IL-6, MIP-2, and KC/GROalpha, NTHI challenge in cigarette smoke-exposed mice led to a prominent up-regulation of a different subset of inflammatory mediators, most notably MCP-1, -3, and -5, IP-10, and MIP-1gamma. This skewed inflammatory mediator expression was also observed after ex vivo NTHI stimulation of alveolar macrophages, signifying their importance to this altered response. Importantly, corticosteroids attenuated inflammation after NTHI challenge in both cigarette smoke-exposed and control mice; however, this was associated with significantly increased bacterial burden. Collectively, these data suggest that cigarette smoke exacerbates the inflammatory response to a bacterial challenge via skewed inflammatory mediator expression.
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ISSN:1073-449X
1535-4970
1535-4970
DOI:10.1164/rccm.200808-1306OC