Early-life co-administration of cockroach allergen and endotoxin augments pulmonary and systemic responses.
BACKGROUND
Environmental exposures to cockroach allergen and endotoxin are recognized epidemiological risk factors for the early development of allergies and asthma in children. Because of this, it is important to examine the role of early-life concurrent inhalation exposures to cockroach allergen and endotoxin in the pathogenesis of allergic airways disease.


OBJECTIVE
We examined the effects of repeated concomitant endotoxin and cockroach allergen inhalation on the pulmonary and systemic immune responses of newborn and juvenile mice.


METHODS
C3H/HeBFeJ mice were exposed to inhaled endotoxin and cockroach allergen via intranasal instillation from day 2 to 21 after birth, and systemic and pulmonary responses were examined in serum, bronchoalveolar lavage fluid, and lung tissue.


RESULTS
Cockroach allergen exposures induced pulmonary eosinophilic inflammation, total and allergen-specific IgE, IgG(1), and IgG(2a) production, and alveolar remodelling. Co-exposures with endotoxin and cockroach allergen significantly increased serum IgE and IgG(1), lung inflammation, and alveolar wall thickness, and decreased airspace volume density. Importantly, compared with exposures with individual substances, the responses to co-exposures were more than additive.


CONCLUSIONS
Repeated inhalation exposures of neonatal and juvenile mice to endotoxin and cockroach allergen increased the pulmonary inflammatory and systemic immune responses in a synergistic manner and enhanced alveolar remodelling in the developing lung. These data underscore the importance of evaluating the effect of multiple, concurrent environmental exposures, and of using an experimental model that incorporates clinically relevant timing and route of exposures.
Environmental Health Sciences Research Center, University of Iowa, Iowa City, IA 52242-5000, USA.
K
K
Kulhankova
C L S
CL
George
J N
JN
Kline
J M
JM
Snyder
M
M
Darling
E H
EH
Field
P S
PS
Thorne
D000485:Allergens / Q000008:administration & dosage* / Q000009:adverse effects* / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn; D001249:Asthma / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D003058:Cockroaches / Q000737:chemistry* / Q000276:immunology; D004195:Disease Models, Animal; D004731:Endotoxins / Q000008:administration & dosage* / Q000009:adverse effects* / Q000276:immunology; D004784:Environmental Monitoring; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008809:Mice, Inbred C3H
D000485:Allergens; D004731:Endotoxins; D007074:Immunoglobulin G; D007073:Immunoglobulin E