Acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza infection, but does not exacerbate deficits in lung function

Abstract

Please cite this paper as: Larcombe et al. (2012) Acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza infection, but does not exacerbate deficits in lung function. Influenza and Other Respiratory Viruses DOI:10.1111/irv.12012. Background Exposure to diesel exhaust particles (DEP) is thought to exacerbate many pre‐existing respiratory diseases, including asthma, bronchitis and chronic obstructive pulmonary disease, however, there is a paucity of data on whether DEP exacerbates illness due to respiratory viral infection. Objectives To assess the physiological consequences of an acute DEP exposure during the peak of influenza‐induced illness. Methods We exposed adult female BALB/c mice to 100 μg DEP (or control) 3·75 days after infection with 104·5 plaque forming units of influenza A/Mem71 (or control). Six hours, 24 hours and 7 days after DEP exposure we measured thoracic gas volume and lung function at functional residual capacity. Bronchoalveolar lavage fluid was taken for analyses of cellular inflammation and cytokines, and whole lungs were taken for measurement of viral titre. Results Influenza infection resulted in significantly increased inflammation, cytokine influx and impairment to lung function. DEP exposure alone resulted in less inflammation and cytokine influx, and no impairment to lung function. Mice infected with influenza and exposed to DEP had higher viral titres and neutrophilia compared with infected mice, yet they did not have more impaired lung mechanics than mice infected with influenza alone. Conclusions A single dose of DEP is not sufficient to physiologically exacerbate pre‐existing respiratory disease caused by influenza infection in mice.

Mechanical Abnormalities of the Airway Wall in Adult Mice After Intrauterine Growth Restriction

“…Respiratory system impedance ( Z rs ) was measured using a wave-tube system (Hantos et al, 1992) adapted for use in small animals (Peták et al, 1997; Sly et al, 2003) and a modification of the forced oscillation technique (Sly et al, 2003; Larcombe et al, 2013). During brief apneic periods, oscillatory signals between 4 and 38 Hz were delivered via a 1-m wave-tube to tracheostomized mice.…”

Viruses and non-allergen environmental triggers in asthma

“…[128][129][130][131] One study looking at DEP exposure and virus titers showed that the combination of DEP and influenza infection results in increased lung neutrophils, increased influenza virus titers, and reduced lung function compared with mice exposed to DEP or influenza alone. 131 In this study lung impairment was not significantly different between DEP/influenza-exposed vs influenza alone-exposed mice, suggesting that the virus infection exerts the most significant lung damage. In vitro studies looking at airway cells exposed to DEP and influenza virus have shown increased oxidative stress, viral replication, and virus attachment in DEP-exposed cells, 132 which may be mediated by enhanced TLR3 pathways.…”

“…Though diesel exhaust, and likely other PM 2.5 matter, alters a person's immune response, the association between DEP and virus infections in humans is not heavily documented. Several murine studies showing altered airway immune responses to virus infections resulting in increased inflammation and/or impaired lung function 128–131. One study looking at DEP exposure and virus titers showed that the combination of DEP and influenza infection results in increased lung neutrophils, increased influenza virus titers, and reduced lung function compared with mice exposed to DEP or influenza alone 131.…”

Geogenic PM10 exposure exacerbates responses to influenza infection

“…The 100 μg dose was chosen based on our previous dose-response data (Zosky et al, 2014a) and prior work on diesel particles (Boylen et al, 2011;Larcombe et al, 2013) showing that particle loads in macrophages are equivalent to those observed in human macrophages (Kulkarni et al, 2006). Control mice received 50 μL of saline alone.…”