Effects Of Staphylococcal Enterotoxin B In The Pathogenesis Of Allergic Rhinitis

OBJECTIVE:Allergic rhinitis is very common. 10-25 percent of the population in the world has allergic rhinitis. Its prevalence is 34.31% in parts of western China. Allergic rhinitis is common diseases which is serious harm to human health and quality of life. The research about the pathogenesis of allergic rhinitis has been a hot subject. Classical theory is that the main mechanism of allergic rhinitis is classified as a typeâ… allergic reaction. Allergen combines with IgE to activate the mast cells. Then the disruption of the mast cells leads to the release of many substances. These substances cause various degrees of nasal mucosal inflammation. But some clinical study has found that the level of serum specific immunoglobulin E was not always related to the severity of symptom. Maybe there is a non-classical way in the pathogenesis of allergic rhinitis. There has recently been much interest in the role of bacterial superantigens in allergic inflammatory reactions. Numerous studies have demonstrated that bacterial superantigens regulate the activity of immuno-modulatory(T lymphocytes) and pro-inflammatory cell types(dendritic cells, eosinophils and epithelial cells etc), and play an important role on allergic disease.Staphylococcal enterotoxin B produced by staphylococcus aureus is a superantigen. Mechanistic studies have shown that superantigens stimulate the T cells by cross-linking the variable part on the beta chain of the T-cell receptor (TCR) with MHC class II molecules outside the peptide-binding groove area. This leads to stimulation of up to 30% of the naive T-cell population in a nonspecific way, compared with stimulation of only about 0.1% of the T cell population via the conventional allergen-specific MHC-restricted route utilizing both TCR-Va and b chains. Thus, direct binding of SEB to an MHC class II molecule loaded with antigen-derived peptides might enhance the antigenicity of the allergen and the development of allergic disease. In addition, SEB may act as allergens. SEB can induce antigen-specific T cells that are able to promote the generation of antigen-specific IgE antibodies, which subsequently play a role in'conventional'allergen-mediated reactions. Humans are natural carriers for staphylococcus aureus, the nasal passage and skin being the most common site for staphylococcus aureus colonization. More than 50% of pathogenic isolates of staphylococcus aureus produce one or more superantigen exotoxins. Given their ability to elaborate superantigen exotoxins and their anatomic localization, it is likely that the nasal passage is exposed to bacterial superantigens. This increases the risk that the atopic individual suffers from allergic disease. But no definitive evidence may demonstrate SEB as allergen can induce allergic rhinitis.In our study, Guinea pigs were intranasally instilled with SEB. The typical symptoms of allergic rhinitis such as sneezing and nasal scratching frequency were evaluated after each intranasal instillation. Eosinophil infiltration in nasal mucosa was observed. The production of antigen-specific antibodies including IgE and IgG1 in serum was measured. Our study may demonstrate that SEB can act as allergen to induce allergic rhinitis.METHODS:20 Hartley guinea pigs were randomly divided into 2 groups: model group and control group(n=10 per group). For model group, guinea pigs were given SEB by intranasal (i.n.) instillation in the absence of adjuvant once every day for 14 times. Prior to each sensitization, the upper airway mucosal surface was anaesthetized by intranasal instillation of 4% lidocaine hydrochloride solution to prevent the rapid elimination of antigen by ciliary movement. One week after the last sensitization, the same treatment was challenged intranasally once every 4 days for 30 times. Prior to each challenge, lidocaine was not used. For the control group, the animals were received the same amount of saline instead of SEB. The typical symptoms of allergic rhinitis such as sneezing and nasal scratching frequency were evaluated after each challenge. SEB-specific antibodies including IgE, IgG1and IgG2 in serum were measured by indirect ELISA. Pathological changed of the nasal mucosa was observed after the nasal mucosa was stained with hematoxylin and eosin.RESULTS:(1) In model group, symptoms of sneezing and nasal scratching were induced after challenge. The serum levels of SEB-specific IgE and IgG1 were higher in model group in comparison with the control group. Intranasal immunization with SEB elicited a local nasal mucosa inflammatory response characterized by apparent eosinophil infiltration. What's more, vasodilatation and oedema is present in the submucosal areas.(2) For the control group, guinea pigs showed few of the typical symptoms of allergic rhinitis. The guinea pigs had no detectable levels of SEB-specific IgE and IgG1 in their sera. The negative results were observed in their nasal mucosa.(3) Compared with the control group, mRNA level of IL-23 in nasal-associated lymphoid tissue showed significantly lower in model group. In addition, the amount of IL-17 in the nasal cavity lavage fluid is lower in model group than the control group.CONCLUSIONS:(1) Repeated intranasal instillation with SEB leads to allergic nasal inflammation. This may demonstrate that SEB can act as conventional allergen to induce allergic rhinitis.(2) Our results show that it is a suitable method to induce the AR animal model with biphasic reaction by repeated intranasal sensitization and challenge with SEB as allergen. This model might be valuable in analyzing the pathogenesis of allergic rhinitis infected with staphylococcus aureus and the late phase nasal reaction.(3) In our study, the expression of the Th17 cytokines such as IL-17 and IL-23 was decreased in model group. But, the amount of IL-4 in the nasal cavity lavage fluid is higher in model group than the control group.This implies that Th2/Th17 cytokine network imbalances appear in allergic rhinitis. The cytokine network imbalances may play an important role in the pathogenesis of allergic rhinitis.