title: Early Life Wildfire Smoke Exposure Is Associated with Immune Dysregulation and Lung Function Decrements in Adolescence.
abstract: The long-term health effects of wildfire smoke exposure in pediatric populations are not known. The objectives of this study were to determine if early life exposure to wildfire smoke can affect parameters of immunity and airway physiology that are detectable with maturity. We studied a mixed-sex cohort of rhesus macaque monkeys that were exposed as infants to ambient wood smoke from a series of Northern California wildfires in the summer of 2008. Peripheral blood mononuclear cells (PBMCs) and pulmonary function measures were obtained when animals were approximately 3 years of age. PBMCs were cultured with either LPS or flagellin, followed by measurement of secreted IL-8 and IL-6 protein. PBMCs from a subset of female animals were also evaluated by Toll-like receptor (TLR) pathway mRNA analysis. Induction of IL-8 protein synthesis with either LPS or flagellin was significantly reduced in PBMC cultures from wildfire smoke-exposed female monkeys. In contrast, LPS- or flagellin-induced IL-6 protein synthesis was significantly reduced in PBMC cultures from wildfire smoke-exposed male monkeys. Baseline and TLR ligand-induced expression of the transcription factor, RelB, was globally modulated in PBMCs from wildfire smoke-exposed monkeys, with additional TLR pathway genes affected in a ligand-dependent manner. Wildfire smoke-exposed monkeys displayed significantly reduced inspiratory capacity, residual volume, vital capacity, functional residual capacity, and total lung capacity per unit of body weight relative to control animals. Our findings suggest that ambient wildfire smoke exposure during infancy results in sex-dependent attenuation of systemic TLR responses and reduced lung volume in adolescence.
authors.affiliation: 1 California National Primate Research Center.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Black
authors.affiliation: 1 California National Primate Research Center.
authors.forename: Joan E
authors.initials: JE
authors.lastname: Gerriets
authors.affiliation: 1 California National Primate Research Center.
authors.forename: Justin H
authors.initials: JH
authors.lastname: Fontaine
authors.affiliation: 2 Division of Pulmonary and Critical Care Medicine, School of Medicine, and.
authors.forename: Richart W
authors.initials: RW
authors.lastname: Harper
authors.affiliation: 2 Division of Pulmonary and Critical Care Medicine, School of Medicine, and.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Kenyon
authors.affiliation: 3 Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California.
authors.forename: Fern
authors.initials: F
authors.lastname: Tablin
authors.affiliation: 3 Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Schelegle
authors.affiliation: 1 California National Primate Research Center.|3 Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Miller
mesh_terms: D000375:Aging / Q000502:physiology*; D000397:Air Pollution / Q000032:analysis; D000818:Animals; D001835:Body Weight; D002140:California; D004781:Environmental Exposure; D005260:Female; D005390:Fires; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008024:Ligands; D016014:Linear Models; D008168:Lung / Q000276:immunology* / Q000503:physiopathology*; D008253:Macaca mulatta; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010316:Particle Size; D052638:Particulate Matter / Q000032:analysis; D012129:Respiratory Function Tests; D012906:Smoke; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D008024:Ligands; D016328:NF-kappa B; D052638:Particulate Matter; D012906:Smoke; D051193:Toll-Like Receptors
keywords: LPS; flagellin; infant; lung; particulate matter; wildfire