Sensitization by subcutaneous route is superior to intraperitoneal route in induction of asthma by house dust mite in a murine mode / Sensibilização por via subcutânea é superior à intraperitoneal na indução de asma por ácaro em modelo murino

ABSTRACT Objective To develop a new experimental model of chronic allergic pulmonary disease induced by house dust mite, with marked production of specific immunoglobulin E (IgE), eosinophilic inflammatory infiltrate in the airways and remodeling, comparing two different routes of sensitization. Methods The protocol lasted 30 days. BALB/c mice were divided into six groups and were sensitized subcutaneously or intraperitoneally with saline (negative control), Dermatophagoides pteronyssinus (Der p) 50 or 500mcg in three injections. Subsequently they underwent intranasal challenge with Der p or saline for 7 days and were sacrificed 24 hours after the last challenge. We evaluated the titration of specific IgE anti-Der p, eosinophilic density in peribronchovascular space and airway remodeling. Results Both animals sensitized intraperitoneally and subcutaneously produced specific IgE anti-Der p. Peribronchovascular eosinophilia increased only in mice receiving lower doses of Der p. However, only the group sensitized with Der p 50mcg through subcutaneously route showed significant airway remodeling. Conclusion In this murine model of asthma, both pathways of sensitization led to the production of specific IgE and eosinophilia in the airways. However, only the subcutaneously route was able to induce remodeling. Furthermore, lower doses of Der p used in sensitization were better than higher ones, suggesting immune tolerance. Further studies are required to evaluate the efficacy of this model in the development of bronchial hyperresponsiveness, but it can already be replicated in experiments to create new therapeutic drugs or immunotherapeutic strategies.

RESUMO Objetivo Desenvolver um novo modelo experimental de doença pulmonar alérgica crônica por ácaro, com proeminente produção de imunoglobulina E (IgE) específica, infiltrado inflamatório eosinofílico nas vias aéreas e remodelamento, comparando duas vias diferentes de sensibilização. Métodos O protocolo teve duração de 30 dias. Camundongos BALB/c foram divididos em seis grupos submetidos à sensibilização por via subcutânea ou intraperitoneal com solução salina (controles negativos),Dermatophagoides pteronyssinus (Der p) 50 ou 500mcg, em três aplicações. Posteriormente, foram submetidos à provocação intranasal com Der p ou salina por 7 dias e sacrificados 24 horas após o último desafio. Avaliamos a titulação de IgE específica anti-Der p, densidade eosinofílica no espaço peribroncovascular e remodelamento das vias aéreas. Resultados Tanto os animais sensibilizados por via subcutânea como intraperitoneal produziram IgE específica anti-Der p. Ocorreu aumento da eosinofilia peribroncovascular apenas nos animais que receberam menor dose de Der p. Porém apenas o grupo sensibilizado com Der p 50mcg subcutânea apresentou remodelamento significativo das vias aéreas. Conclusão Neste modelo murino de asma, as duas vias de sensibilização levaram à produção de IgE específica e eosinofilia nas vias aéreas. No entanto, apenas a via subcutânea foi capaz de induzir ao remodelamento. Além disso, doses menores de Der p utilizadas foram superiores às mais elevadas, sugerindo tolerância. Mais estudos são necessários para avaliar a eficácia deste modelo no desenvolvimento da hiperresponsividade brônquica, mas ele pode ser replicado em experimentos para criação de novas estratégias terapêuticas medicamentosas ou imunoterápicas.

Decrease in passive cutaneous anaphylaxis reactions in rats secondary to stress

Anaphylaxis was assayed by the passive cutaneous anaphylaxis (PCA) test in male Wistar rats (250 g body weight). Three experimental groups were used: animals restrained in an electric chamber and submitted to electric shock immediately after sensitization and 24 h before anaphylaxis (31 animals), animals restrained in the electric chamber for the same time but receiving no electric shock (23 animals), and non-manipulated, home-cage control animals (24 animals). The frequency of PCA reactions was decreased in the group of animals submitted to restraint when compared with the home-cage control group. However, the group of animals submitted to both restraint and electric shock showed no decrease in the frequency of PCA reactions. It is suggested that, in rats, stress induced by restraint decreases PCA reactions and that this decrease is counteracted by a simultaneous stress induced by electric shock

Effect of purified components of Ascaris suum extracts on IgE antibody response in guinea pigs

The effect of components P530 and P29, isolated from Ascaris suum adult worm extract (ASC), on the heterologous IgE antibody response was studied in guinea pigs. Groups of 7 guinea pigs were immunized ip with 50 micrograms of ovalbumin (OA) alone or mixed with 200 micrograms of each component precipitated in an alum gel. The primary and secondary IgE antibody response was evaluated by passive cutaneous anaphylaxis reaction (PCA). Immunization of guinea pigs with P29 plus ovalbumin (OA) resulted in a significant increase in the level of serum IgE anti-OA antibodies, especially in the secondary response (almost 8-fold higher when compared with control group). This potentiated response was not observed when the animals received OA plus P530 or the crude extract. Indeed, the P530 component, as well as the crude extract, induced a depression of the anti-OA IgE antibody response (2-3 fold decrease when compared with OA-immunized animals). It was also shown that P29, but not P530 or ASC, was capable of eliciting a strong anti-ASC IgE antibody response. These results demonstrate that in guinea pigs these two Ascaris suum components have antagonistic biological effects, one inducing potentiation and the other suppression of the heterologous IgE antibody response