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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Vydáno v:	American journal of respiratory and critical care medicine Ročník 179; číslo 8; s. 666 - 675
Hlavní autoři:	Gaschler, Gordon J, Skrtic, Marko, Zavitz, Caleb C. J, Lindahl, Maria, Onnervik, Per-Ola, Murphy, Timothy F, Sethi, Sanjay, Stampfli, Martin R
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York, NY Am Thoracic Soc 15.04.2009 American Thoracic Society
Témata:	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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1073-449X 1535-4970 1535-4970
DOI:	10.1164/rccm.200808-1306OC