Immunomodulatory effects of IL-12 on allergic lung inflammation depend on timing of doses.

Abstract

We investigated the effects of IL-12 on a murine model of allergic lung inflammation. Administration of IL-12 was timed to interfere with either allergic sensitization (early dosage) or the hypersensitivity inflammatory response in the lung (late dosage), or both (early and late dosages). Comparisons of IL-12- and PBS-treated animals within each treatment group revealed several noticeable effects of IL-12. Early dosage, and the combination of early and late dosages, strikingly decreased ragweed-specific serum IgE, tracheal ring reactivity to acetylcholine, and BAL eosinophilia following allergen challenge. In contrast, late dosage had no effect on IgE levels and only a minimal effect on tracheal ring reactivity, but had a modest effect on recruitment of eosinophils. Early dosage down-regulated IL-5 and IL-10, but did not alter IL-4 or IFN-gamma expression. Late dosage down-regulated IL-5, up-regulated IL-10 and IFN-gamma, but did not change IL-4 expression. The combination of early and late dosage down-regulated IL-4, IL-5, and IL-10 expression, but increased IFN-gamma expression and production in the BAL cells and fluids. Taken together, these results indicate that IL-12 has potent immunomodulatory effects on allergic lung inflammation that depend on the timing of IL-12 administration relative to allergic sensitization and allergen challenge.

A recombinant fragment of human SP-D reduces allergic responses in mice sensitized to house dust mite allergens

“…The reduction in peripheral blood eosinophilia observed in the present study is consistent with an up-regulation of IL-12 and IFN-g. Sur et al showed that administration of IL-12 decreased allergen-induced lung eosinophilia in a murine model of ragweed allergy [32]. Similar effects were found when as little as 0•1 mg/day was given to D. pteronyssinus-sensitized mice [8].…”

“…Sur et al . showed that administration of IL‐12 decreased allergen‐induced lung eosinophilia in a murine model of ragweed allergy [32]. Similar effects were found when as little as 0·1 µ g/day was given to D. pteronyssinus ‐sensitized mice [8].…”

Influencia da obesidade no desenvolvimento da asma alergica experimental

“…Diversos protocolos de indução da asma têm sido publicados utilizando variados tipos de antígenos, vias de aplicação, doses e tempos de avaliação. Os antígenos aplicados em modelos animais incluem alguns dos quais estão freqüentemente associados com a asma em humanos, tais como pó ou poeira, alimentos e fungos, ao passo que muitos utilizam a ovalbumina (OVA) mesmo com pouca relevância clínica (Yssel et al, 1992;Sur et al, 1996;Lewkowich et al, 2005). O procedimento freqüentemente utilizado em modelos animais é a indução de um estado alérgico, frente ao uso de antígeno conhecido, como a OVA, onde normalmente se empregam 2 injeções deste alergeno associado ao alúmen (hidróxido de alumínio).…”