Allergic inflammation does not impact chemical-induced carcinogenesis in the lungs of mice.
BACKGROUND
Although the relationship between allergic inflammation and lung carcinogenesis is not clearly defined, several reports suggest an increased incidence of lung cancer in patients with asthma. We aimed at determining the functional impact of allergic inflammation on chemical carcinogenesis in the lungs of mice.


METHODS
Balb/c mice received single-dose urethane (1 g/kg at day 0) and two-stage ovalbumin during tumor initiation (sensitization: days -14 and 0; challenge: daily at days 6-12), tumor progression (sensitization: days 70 and 84; challenge: daily at days 90-96), or chronically (sensitization: days -14 and 0; challenge: daily at days 6-12 and thrice weekly thereafter). In addition, interleukin (IL)-5 deficient and wild-type C57BL/6 mice received ten weekly urethane injections. All mice were sacrificed after four months. Primary end-points were number, size, and histology of lung tumors. Secondary end-points were inflammatory cells and mediators in the airspace compartment.


RESULTS
Ovalbumin provoked acute allergic inflammation and chronic remodeling of murine airways, evident by airspace eosinophilia, IL-5 up-regulation, and airspace enlargement. Urethane resulted in formation of atypical alveolar hyperplasias, adenomas, and adenocarcinomas in mouse lungs. Ovalbumin-induced allergic inflammation during tumor initiation, progression, or continuously did not impact the number, size, or histologic distribution of urethane-induced pulmonary neoplastic lesions. In addition, genetic deficiency in IL-5 had no effect on urethane-induced lung tumorigenesis.


CONCLUSIONS
Allergic inflammation does not impact chemical-induced carcinogenesis of the airways. These findings suggest that not all types of airway inflammation influence lung carcinogenesis and cast doubt on the idea of a mechanistic link between asthma and lung cancer.
Doris
Konstantinos
K
Applied Biomedical Research & Training Center Marianthi Simou, Department of Critical Care & Pulmonary Services, General Hospital Evangelismos, School of Medicine, National and Kapodistrian University of Athens, 3 Ploutarhou Str, 10675 Athens, Greece.
Karabela
Sophia P
SP
Kairi
Chrysoula A
CA
Simoes
Davina Cm
DC
Roussos
Charis
C
Zakynthinos
Spyros G
SG
Kalomenidis
Ioannis
I
Blackwell
Timothy S
TS
Stathopoulos
Georgios T
GT
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015197:Carcinogenicity Tests / Q000379:methods; D004195:Disease Models, Animal; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011897:Random Allocation; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology*; D014520:Urethane / Q000633:toxicity
D014520:Urethane
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