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Effect of Woodsmoke Particle Exposure on Antiviral Host Defense in Human Volunteers: Nasal Inflammatory Mediators and Influence of Gender on Responses
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A4165 - Effect of Woodsmoke Particle Exposure on Antiviral Host Defense in Human Volunteers: Nasal Inflammatory Mediators and Influence of Gender on Responses
Author Block: T. L. Noah1, M. Rebuli2, A. M. Speen2, C. Robinette2, I. Jaspers1; 1Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, 2Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
RATIONALE. Exposure of the respiratory tract to particulates from burning biomass is an increasing global health issue linked to climate change and population growth. We have previously reported the effects of cigarette smoking and diesel exhaust on nasal responses to influenza virus. We hypothesized that acute exposure to woodsmoke particles (WSP) would suppress nasal cytokine responses to influenza.
METHODS. Healthy nonsmoking young adult volunteers were randomized to a 2-hr controlled chamber exposure to WSP (500 μg/cm3) generated from smoldering red oak, or clean air as control, then both groups were inoculated nasally with a standard vaccine dose of live attenuated influenza virus (LAIV). Nasal lavage was performed at pre-exposure baseline (day 0), and on day 1, day 2, and day 7 post-exposure. Nasal lavage fluid (NLF) cells were analyzed for inflammatory gene expression profiles and cell-free NLF were assayed for cytokines and chemokines by multiplex ELISA.
RESULTS. In both the WSP (N=20) and control (N=19) exposure groups, LAIV induced expected transient increases in inflammatory (IL-6) and antiviral (IFNɣ) responses. Viral sequence quantity in NLF cells did not differ between WSP and control, but 4 of 20 WSP reported mild flu-like or upper respiratory symptoms, compared to only 1 of 19 controls. Among the panel of 30 cytokines and chemokines measured in NLF, more than half were significantly higher at baseline in males than in females. Only IL-10 was significantly affected by WSP exposure, with suppressed Day 2 response in WSP exposed subjects (median 0.9 fold change from baseline, interquartile 0.5-1.7) compared to controls (2.8 fold change, interquartile 0.9-6.2) (P=0.03). WSP-associated suppression of IL-10 receptor (IL10RB) was also noted in gene expression profiles from NLF cells (median 5.8 log2 fold decrease in WSP vs. control; P=0.001), and was more prominent in male subjects.
CONCLUSIONS. A 2-hour exposure to 500 μg/cm3 WSP was associated with suppression of post-LAIV IL-10 response in nasal secretions as well as IL10RB gene expression in NLF cells. Of note, we observed significant gender related differences in both baseline nasal mediators and in response patterns to LAIV and WSP. While the importance of these observations for human health is unclear, we speculate that WSP-induced suppression of IL-10 might delay resolution of virus-induced respiratory inflammation, resulting in enhanced symptoms and risk for post viral infection complications in susceptible individuals. Gender should be considered as a variable in studies of particulate respiratory health effects.
Funded by: NIH 5R01ES013611
Author Block: T. L. Noah1, M. Rebuli2, A. M. Speen2, C. Robinette2, I. Jaspers1; 1Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, 2Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
RATIONALE. Exposure of the respiratory tract to particulates from burning biomass is an increasing global health issue linked to climate change and population growth. We have previously reported the effects of cigarette smoking and diesel exhaust on nasal responses to influenza virus. We hypothesized that acute exposure to woodsmoke particles (WSP) would suppress nasal cytokine responses to influenza.
METHODS. Healthy nonsmoking young adult volunteers were randomized to a 2-hr controlled chamber exposure to WSP (500 μg/cm3) generated from smoldering red oak, or clean air as control, then both groups were inoculated nasally with a standard vaccine dose of live attenuated influenza virus (LAIV). Nasal lavage was performed at pre-exposure baseline (day 0), and on day 1, day 2, and day 7 post-exposure. Nasal lavage fluid (NLF) cells were analyzed for inflammatory gene expression profiles and cell-free NLF were assayed for cytokines and chemokines by multiplex ELISA.
RESULTS. In both the WSP (N=20) and control (N=19) exposure groups, LAIV induced expected transient increases in inflammatory (IL-6) and antiviral (IFNɣ) responses. Viral sequence quantity in NLF cells did not differ between WSP and control, but 4 of 20 WSP reported mild flu-like or upper respiratory symptoms, compared to only 1 of 19 controls. Among the panel of 30 cytokines and chemokines measured in NLF, more than half were significantly higher at baseline in males than in females. Only IL-10 was significantly affected by WSP exposure, with suppressed Day 2 response in WSP exposed subjects (median 0.9 fold change from baseline, interquartile 0.5-1.7) compared to controls (2.8 fold change, interquartile 0.9-6.2) (P=0.03). WSP-associated suppression of IL-10 receptor (IL10RB) was also noted in gene expression profiles from NLF cells (median 5.8 log2 fold decrease in WSP vs. control; P=0.001), and was more prominent in male subjects.
CONCLUSIONS. A 2-hour exposure to 500 μg/cm3 WSP was associated with suppression of post-LAIV IL-10 response in nasal secretions as well as IL10RB gene expression in NLF cells. Of note, we observed significant gender related differences in both baseline nasal mediators and in response patterns to LAIV and WSP. While the importance of these observations for human health is unclear, we speculate that WSP-induced suppression of IL-10 might delay resolution of virus-induced respiratory inflammation, resulting in enhanced symptoms and risk for post viral infection complications in susceptible individuals. Gender should be considered as a variable in studies of particulate respiratory health effects.
Funded by: NIH 5R01ES013611
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