Allergic sensitization is associated with inadequate anti-oxidant responses in mice and men

Abstract

BACKGROUND: Allergies arise from aberrant Th2 responses to allergens. The processes involved in the genesis of allergic sensitization remain elusive. Some allergens such as derived from house dust mites, have proteolytic activity which can induce oxidative stress in vivo. A reduced capacity of the host to control oxidative stress might prime for allergic sensitization. METHODS: Two different strains of mice were compared for their anti-oxidant and immune response to HDM. Protease activity of the HDM extract was reduced to investigate its role in oxidative stress induction in the airways and whether this induction could determine allergic sensitization and inflammation. The role of oxidative stress in allergic sensitization was also investigated in humans. An occupational cohort of animal workers was followed for development of sensitization to rodent urinary proteins. Levels of oxidative stress in serum and anti-oxidant responses by PBMCs were determined. RESULTS: Susceptibility to allergic sensitization to mite allergens in mice was highly dependent on host genetic background and was associated with oxidative stress in the lungs before allergen exposure and poor anti-oxidant response after allergen exposure. Reduction of mite protease activity limited its capacity to induce oxidative stress and allergic inflammation in mice. We showed that also in human subjects, oxidative stress before allergen exposure and poor anti-oxidant responses were associated with predisposition to occupational allergy. CONCLUSION: Our study indicates that oxidative stress condition before allergen exposure due to an inadequate anti-oxidant response primes for allergic Th2 responses. This article is protected by copyright. All rights reserved.