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Cigarette smoke worsens lung inflammation and impairs resolution of influenza infection in mice.

Gualano RC, Hansen MJ, Vlahos R, Jones JE, Park-Jones RA, Deliyannis G, Turner SJ, Duca KA, Anderson GP - Respir. Res. (2008)

Bottom Line: Cigarette smoke has both pro-inflammatory and immunosuppressive effects.Smoke induced inflammation does not protect against influenza infection.In most respects, smoke exposure worsened the host response to influenza.This animal model may be useful in studying how smoke worsens respiratory viral infections.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology, The University of Melbourne, Parkville 3010, Victoria, Australia. rgualano@unimelb.edu.au

ABSTRACT

Background: Cigarette smoke has both pro-inflammatory and immunosuppressive effects. Both active and passive cigarette smoke exposure are linked to an increased incidence and severity of respiratory virus infections, but underlying mechanisms are not well defined. We hypothesized, based on prior gene expression profiling studies, that upregulation of pro-inflammatory mediators by short term smoke exposure would be protective against a subsequent influenza infection.

Methods: BALB/c mice were subjected to whole body smoke exposure with 9 cigarettes/day for 4 days. Mice were then infected with influenza A (H3N1, Mem71 strain), and analyzed 3 and 10 days later (d3, d10). These time points are the peak and resolution (respectively) of influenza infection.

Results: Inflammatory cell influx into the bronchoalveolar lavage (BALF), inflammatory mediators, proteases, histopathology, viral titres and T lymphocyte profiles were analyzed. Compared to smoke or influenza alone, mice exposed to smoke and then influenza had more macrophages, neutrophils and total lymphocytes in BALF at d3, more macrophages in BALF at d10, lower net gelatinase activity and increased activity of tissue inhibitor of metalloprotease-1 in BALF at d3, altered profiles of key cytokines and CD4+ and CD8+ T lymphocytes, worse lung pathology and more virus-specific, activated CD8+ T lymphocytes in BALF. Mice smoke exposed before influenza infection had close to 10-fold higher lung virus titres at d3 than influenza alone mice, although all mice had cleared virus by d10, regardless of smoke exposure. Smoke exposure caused temporary weight loss and when smoking ceased after viral infection, smoke and influenza mice regained significantly less weight than smoke alone mice.

Conclusion: Smoke induced inflammation does not protect against influenza infection.In most respects, smoke exposure worsened the host response to influenza. This animal model may be useful in studying how smoke worsens respiratory viral infections.

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Related in: MedlinePlus

Flow cytometry quantitation of T lymphocytes. CD3+ CD4+ lymphocytes in (a) BALF & (b) LNs, and CD3+ CD8+ lymphocytes in (c) BALF and (d) LNs were quantitated by flow cytometry. Clear boxes denote mice not infected with influenza and dark boxes denote mice infected with influenza. The y-axis counts represent the total figure for the pooled samples of 8 mice per treatment. Figure 6(e) is a histogram presentation of CD4+CD25+ and CD8+ CD25+ cells in BALF (pooled samples of 8 mice per group), with and without smoke exposure.
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Figure 6: Flow cytometry quantitation of T lymphocytes. CD3+ CD4+ lymphocytes in (a) BALF & (b) LNs, and CD3+ CD8+ lymphocytes in (c) BALF and (d) LNs were quantitated by flow cytometry. Clear boxes denote mice not infected with influenza and dark boxes denote mice infected with influenza. The y-axis counts represent the total figure for the pooled samples of 8 mice per treatment. Figure 6(e) is a histogram presentation of CD4+CD25+ and CD8+ CD25+ cells in BALF (pooled samples of 8 mice per group), with and without smoke exposure.

Mentions: Some key types of T cells were quantitated in BALF and LNs by FACS. Smoke and influenza mice had fewer CD3+ CD4+ (helper T) lymphocytes and CD3+ CD8+ (cytotoxic T lymphocytes) in their LNs, at both d3 and d10, than influenza alone mice (Figures 6b and 6d). However, at d10, smoke and influenza mice had many more CD4+ and CD8+ T cells in BALF, than influenza alone mice (Figures 6a and 6c). Smoke alone mice had more CD4+ T cells in BALF at d10 than no treatment mice.


Cigarette smoke worsens lung inflammation and impairs resolution of influenza infection in mice.

Gualano RC, Hansen MJ, Vlahos R, Jones JE, Park-Jones RA, Deliyannis G, Turner SJ, Duca KA, Anderson GP - Respir. Res. (2008)

Flow cytometry quantitation of T lymphocytes. CD3+ CD4+ lymphocytes in (a) BALF & (b) LNs, and CD3+ CD8+ lymphocytes in (c) BALF and (d) LNs were quantitated by flow cytometry. Clear boxes denote mice not infected with influenza and dark boxes denote mice infected with influenza. The y-axis counts represent the total figure for the pooled samples of 8 mice per treatment. Figure 6(e) is a histogram presentation of CD4+CD25+ and CD8+ CD25+ cells in BALF (pooled samples of 8 mice per group), with and without smoke exposure.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2483272&req=5

Figure 6: Flow cytometry quantitation of T lymphocytes. CD3+ CD4+ lymphocytes in (a) BALF & (b) LNs, and CD3+ CD8+ lymphocytes in (c) BALF and (d) LNs were quantitated by flow cytometry. Clear boxes denote mice not infected with influenza and dark boxes denote mice infected with influenza. The y-axis counts represent the total figure for the pooled samples of 8 mice per treatment. Figure 6(e) is a histogram presentation of CD4+CD25+ and CD8+ CD25+ cells in BALF (pooled samples of 8 mice per group), with and without smoke exposure.
Mentions: Some key types of T cells were quantitated in BALF and LNs by FACS. Smoke and influenza mice had fewer CD3+ CD4+ (helper T) lymphocytes and CD3+ CD8+ (cytotoxic T lymphocytes) in their LNs, at both d3 and d10, than influenza alone mice (Figures 6b and 6d). However, at d10, smoke and influenza mice had many more CD4+ and CD8+ T cells in BALF, than influenza alone mice (Figures 6a and 6c). Smoke alone mice had more CD4+ T cells in BALF at d10 than no treatment mice.

Bottom Line: Cigarette smoke has both pro-inflammatory and immunosuppressive effects.Smoke induced inflammation does not protect against influenza infection.In most respects, smoke exposure worsened the host response to influenza.This animal model may be useful in studying how smoke worsens respiratory viral infections.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology, The University of Melbourne, Parkville 3010, Victoria, Australia. rgualano@unimelb.edu.au

ABSTRACT

Background: Cigarette smoke has both pro-inflammatory and immunosuppressive effects. Both active and passive cigarette smoke exposure are linked to an increased incidence and severity of respiratory virus infections, but underlying mechanisms are not well defined. We hypothesized, based on prior gene expression profiling studies, that upregulation of pro-inflammatory mediators by short term smoke exposure would be protective against a subsequent influenza infection.

Methods: BALB/c mice were subjected to whole body smoke exposure with 9 cigarettes/day for 4 days. Mice were then infected with influenza A (H3N1, Mem71 strain), and analyzed 3 and 10 days later (d3, d10). These time points are the peak and resolution (respectively) of influenza infection.

Results: Inflammatory cell influx into the bronchoalveolar lavage (BALF), inflammatory mediators, proteases, histopathology, viral titres and T lymphocyte profiles were analyzed. Compared to smoke or influenza alone, mice exposed to smoke and then influenza had more macrophages, neutrophils and total lymphocytes in BALF at d3, more macrophages in BALF at d10, lower net gelatinase activity and increased activity of tissue inhibitor of metalloprotease-1 in BALF at d3, altered profiles of key cytokines and CD4+ and CD8+ T lymphocytes, worse lung pathology and more virus-specific, activated CD8+ T lymphocytes in BALF. Mice smoke exposed before influenza infection had close to 10-fold higher lung virus titres at d3 than influenza alone mice, although all mice had cleared virus by d10, regardless of smoke exposure. Smoke exposure caused temporary weight loss and when smoking ceased after viral infection, smoke and influenza mice regained significantly less weight than smoke alone mice.

Conclusion: Smoke induced inflammation does not protect against influenza infection.In most respects, smoke exposure worsened the host response to influenza. This animal model may be useful in studying how smoke worsens respiratory viral infections.

Show MeSH
Related in: MedlinePlus