Prenatal allergen exposures prevent allergen-induced sensitization and airway inflammation in young mice.

BACKGROUND: Immune-modulation such as tolerance induction appears to be an upcoming concept to prevent development of atopic diseases. Pregnancy might present a critical period for preventing allergic sensitization of the progeny. We investigated the effect of maternal allergen exposures during pregnancy on allergen-induced sensitization and airway inflammation in the offspring in a murine model. METHODS: BALB/c mice were exposed to aerosolized ovalbumin (OVA) three times per week from day 7 of pregnancy until delivery (day 0). Offspring were systemically sensitized by six intraperitoneal injections with OVA between postnatal days 21 and 35, prior to airway allergen challenges on days 48, 49, and 50. Analyses were performed on day 52. To examine long-lasting effects of maternal OVA exposures some offspring were sensitized between days 115 and 129; analyses took place on day 147. RESULTS: Compared to maternal placebo exposures, maternal OVA exposures suppressed OVA-specific IgE serum levels and inhibited development of allergen-induced airway inflammation in the OVA-sensitized offspring on both days 52 and 147. This protective effect was associated with a shift from a predominant Th2 immune response toward a predominant production of the cytokines IFN-γ and IL-10. Further, maternal OVA exposures were associated with development of CD25(+) Foxp3(+) regulatory T cells (T(regs)) in the OVA-sensitized offspring. Depletion of T(regs) or neutralization of IL-10 prior to allergen sensitization re-established OVA-induced sensitization and eosinophilic airway inflammation in the OVA-sensitized offspring. CONCLUSIONS: In our model, maternal allergen exposures during pregnancy prevented later allergen-mediated sensitization and airway inflammation by allergen-specific tolerance induction in the offspring.

Eosinophilic nasal polyps are a rich source of eotaxin, eotaxin-2 and eotaxin-3.

INTRODUCTION: The CC-chemokine eotaxin plays a key role in the pathologic mechanism of tissue eosinophilia in nasal polyposis. In this study, we investigated a possible role of eotaxin-2 and eotaxin-3, the recently discovered members of the eotaxin family. METHODS: Nasal polyps from 24 patients (non allergic/allergic/aspirin-intolerant patients) and turbinate tissue from 8 controls were investigated. Chemokine protein content (eotaxin, eotaxin-2, and -3) of tissue homogenates was measured by ELISA. Paraffin sections of samples were stained to determine the extent of eosinophilia. RESULTS: Protein expression of eotaxin, eotaxin-2 and eotaxin-3 was significantly higher in nasal polyps than in controls. There was a direct correlation between the protein concentrations of all three eotaxins. Further, protein levels of all chemokines were significantly correlated to the amount of eosinophilia. In aspirin-sensitive polyps the number of eosinophils was significantly higher than in the other patient groups and they had significantly higher eotaxin, eotaxin-2, and -3 protein levels than non-allergic and significantly higher amounts of eotaxin-3 compared with allergic patients. CONCLUSIONS: Our findings suggest, that all members of the eotaxin family are involved in the pathogenesis of nasal polyposis. The results are more likely indicative of a complex cooperation between all members of the eotaxin family than of a specific role in the development of eosinophilia and nasal polyposis.