TY - JOUR
T1 - Ambient PM2.5 and specific sources increase inflammatory cytokine responses to stimulators and reduce sensitivity to inhibitors
AU - Miller, Gregory E.
AU - Passarelli, Veronica
AU - Chen, Edith
AU - Kloog, Itai
AU - Wright, Rosalind J.
AU - Amini, Heresh
N1 - Publisher Copyright:
© 2024 Elsevier Inc.
PY - 2024/7/1
Y1 - 2024/7/1
N2 - Ambient exposure to fine particulate matter (PM2.5) is associated with increased morbidity and mortality from multiple diseases. Recent observations suggest the hypothesis that trained immunity contributes to these risks, by demonstrating that ambient PM2.5 sensitizes innate immune cells to mount larger inflammatory response to subsequent bacterial stimuli. However, little is known about how general and durable this sensitization phenomenon is, and whether specific sources of PM2.5 are responsible. Here we consider these issues in a longitudinal study of children. The sample consisted of 277 children (mean age 13.92 years; 63.8% female; 38.4% Black; 32.2% Latinx) who completed baseline visits and were re-assessed two years later. Fasting whole blood was ex vivo incubated with 4 stimulating agents reflecting microbial and sterile triggers of inflammation, and with 2 inhibitory agents, followed by assays for IL-1β, IL-6, IL-8, and TNF-α. Blood also was assayed for 6 circulating biomarkers of low-grade inflammation: C-reactive protein, interleukin-6, -8, and -10, tumor necrosis factor-α, and soluble urokinase-type plasminogen activator receptor. Using machine learning, levels of 15 p.m.2.5 constituents were estimated for a 50 m grid around children's homes. Models were adjusted for age, sex, race, pubertal status, and household income. In cross-sectional analyses, higher neighborhood PM2.5 was associated with larger cytokine responses to the four stimulating agents. These associations were strongest for constituents released by motor vehicles and soil/crustal dust. In longitudinal analyses, residential PM2.5 was associated with declining sensitivity to inhibitory agents; this pattern was strongest for constituents from fuel/biomass combustion and motor vehicles. By contrast, PM2.5 constituents were not associated with the circulating biomarkers of low-grade inflammation. Overall, these findings suggest the possibility of a trained immunity scenario, where PM2.5 heightens inflammatory cytokine responses to multiple stimulators, and dampens sensitivity to inhibitors which counter-regulate these responses.
AB - Ambient exposure to fine particulate matter (PM2.5) is associated with increased morbidity and mortality from multiple diseases. Recent observations suggest the hypothesis that trained immunity contributes to these risks, by demonstrating that ambient PM2.5 sensitizes innate immune cells to mount larger inflammatory response to subsequent bacterial stimuli. However, little is known about how general and durable this sensitization phenomenon is, and whether specific sources of PM2.5 are responsible. Here we consider these issues in a longitudinal study of children. The sample consisted of 277 children (mean age 13.92 years; 63.8% female; 38.4% Black; 32.2% Latinx) who completed baseline visits and were re-assessed two years later. Fasting whole blood was ex vivo incubated with 4 stimulating agents reflecting microbial and sterile triggers of inflammation, and with 2 inhibitory agents, followed by assays for IL-1β, IL-6, IL-8, and TNF-α. Blood also was assayed for 6 circulating biomarkers of low-grade inflammation: C-reactive protein, interleukin-6, -8, and -10, tumor necrosis factor-α, and soluble urokinase-type plasminogen activator receptor. Using machine learning, levels of 15 p.m.2.5 constituents were estimated for a 50 m grid around children's homes. Models were adjusted for age, sex, race, pubertal status, and household income. In cross-sectional analyses, higher neighborhood PM2.5 was associated with larger cytokine responses to the four stimulating agents. These associations were strongest for constituents released by motor vehicles and soil/crustal dust. In longitudinal analyses, residential PM2.5 was associated with declining sensitivity to inhibitory agents; this pattern was strongest for constituents from fuel/biomass combustion and motor vehicles. By contrast, PM2.5 constituents were not associated with the circulating biomarkers of low-grade inflammation. Overall, these findings suggest the possibility of a trained immunity scenario, where PM2.5 heightens inflammatory cytokine responses to multiple stimulators, and dampens sensitivity to inhibitors which counter-regulate these responses.
KW - Air pollution
KW - Children
KW - Cytokines
KW - Inflammation
KW - PM components
UR - http://www.scopus.com/inward/record.url?scp=85190751020&partnerID=8YFLogxK
U2 - 10.1016/j.envres.2024.118964
DO - 10.1016/j.envres.2024.118964
M3 - Article
C2 - 38640989
AN - SCOPUS:85190751020
SN - 0013-9351
VL - 252
JO - Environmental Research
JF - Environmental Research
M1 - 118964
ER -