The Effect Of Early Exposure To Allergen On Mouse Allergic Rhinitis Model

Allergic rhinitis is a common allergic disease, the incidence rasing perpetualy, thepathogensy has not elucidation yet, and the treatment is limited,mainly concluds allergenavoiding, drug treatment and specific immune therpy, but these therapeutics havedisadvantages in clinical manipuility and long-term, shot-term effects.besides the specificimmune therpy,in recent years, also raise to a number of new non-specific immune therapy,such as IgE monoclonal antibody, gene therapy, transfer factor, mycobacteria vaccinum, etal., but still in reserch,the clinical efficacy has not yet been determined. At the same time inactively looking for more effective treament to allergic rhinitis, studies of AR put the focuson the prevention, especially in gestation,neonatal and childhood stages,but the conclusionis not unform. So we made the assumption that, preventivlly vaccinate allergen on earlystage, and then observe the development of the allergic rhinitis in adult and theimmunological changes in vivo, whether to produce the protective effect.In the first part of the reserch, to investigate the cytokine level in the supernatants ofspleen cell stimulated with different stimulus of allergic rhinitis model at different time,compared the effect of the two stimulus to the cytokine, and its secrete status. We sensitizedand challenged the BALB/c mice with ovalbumin(OVA), in the control group used normalsodium instead of OVA, after the last challenge we cultured the spleen mononuclear cell(SMNC) and stimulated with OVA or concanavlinA (ConA), then got the supernatants ofthe SMNC cultures at 24h, 48h and 72h respectively to measure the concentration ofcytokine IL-4, IL-5 and IFN-?.We obtained splenic lymphocyte (SPL) and stimulated withOVA or ConA, 72h later determined growth rate of the SPL. Splenic lymphocyte sensitizedwith OVA or ConA striking proliferated, the stimulation index (SI) showed significantdeviation with control group (P?0.05). Production of IL-4, IL-5 and IFN-?byConA-stimulated SMNC from sensitized mice increased significantly(P?0.05); theconcentration of IL-4 and IL-5 by OVA-stimulated SMNC from sensitized mice alsoincreased, inversely the production of IFN-?resulted suppression. The level of IL-4 wasincreased obviously in 72 hours, IL-5 and IFN-?were increased significantly in 48 hours,and slow down from 48 to 72 hours. The T cells of the experimental allergic rhinitis mice were generally activated. Production of cytokines from Th2 cells by OVA or ConAincreased sibnificantly, but Th1 cells and its cytokines were suppressed. The result is moreobvious in the ConA-stimulated group. The levels of cytokines increased persistantlywithin 72 hours, but with different amplitude in different time.In the second part of the research, to investigate the effect of the early exposure toallergen on the development of allergic rhinitis, we subcutaneous inject mice of differentdoses of allergen with different kinds of immune adjuvant in different development stages.By detecting specific immunoglobulin in serum and spleen cell culture supernatant levels ofcytokines in order to observe the adult allergic rhinitis in vivo immune status, to reflect theearly antigen vaccination can reduce the allergic rhinitis in vivo immune response, to reflectthe early antigen vaccination can reduce the allergic rhinitis in vivo immune response, thatis, whether the occurrence of allergic rhinitis has a protective effect on.Through fourperiods: pre-pregnancy, pregnancy, newborn, childhood we found:1. allergen subcutaneous injection in the period of preprogation,its generationssensitized and stimulated with allergens, detect the level of antigen-specificantibodies,and related cytokines,we found, 10?gOVA by subcutaneous injection ofdifferent adjuvant at pregastation, to stimulate their descendants after sensitization in vivoOVA-specific IgE levels were significantly reduced, with the positive control group weresignificantly different, the OVA-specific IgG and IgG2a levels were significantly higherthan other groups, the corresponding cytokine levels of IL-4 is also a significant reduction,and IL-10 and IFN-r level was significantly higher. Note to future generations 10?gOVApre-injection in mice of the occurrence and development of allergic rhinitis have asignificant protective effect. Group 1000#gOVA the level of OVA-specific IgE than thepositive control group, but higher than the 10?g dose group, but the protective effect that isless than low-dose group, and future generations 100?gOVA group mice showedimmunological indicator of weak or no protective effect protective effect.2. Subcutaneous injection of allergen during pregnancy to observe the offspring ofmice. Each dose group and above the differences between the results of pre-pregnancysimilar to 10?g dose group also showed a clear protective effect, 1000?g dose group wasfollowed, 100?g dose group protective effect of the weak or non-protective effect. However, different to pre-pregnancy, in pregnancy high-dose subcutaneous injection of allergen(1000?g) with Freund's adjuvant, pregnant mice lead to miscarriage, stillbirth, teratogenic,high mortality in newborn mice, and therefore is not recommended during pregnancy givenhigh-dose allergen immunization.3. Subcutaneous injection of newborn mice allergens, allergens stimulate untiladulthood and found that doses of 100?g and 1000?g group of OVA-specific IgE levelswere significantly reduced, with the positive control group were significantly different,100?g dose of OVA-specific IgG levels were significantly higher than other groups, thecorresponding cytokine levels of IL-4 reduced, IFN-r increase; 10?g dose group the resultsof the contrary, that the newborn mice, subcutaneous injection of 100 or 1000?g allergen itsoccurrence and development of allergic rhinitis have protective effect, while the protectiveeffect of small doses of weak or no protective effect.4. Juvenile mice subcutaneous injection of allergen and found OVA-IgE and IL-4level with the allergen dose gradually to reduce the increase, while IL-10 and IFN-r level isgradually increased on injection of large juvenile dose of antigen may have a protectiveeffect on their, and the injection of the principle of low-dose anti-protective effects of weakor no protective effect.Fully mechanized, the different times and different doses of allergen in mice immuneto the impact of state is different, the immune system as a result of various factors in vivointeraction of different immune response to different doses of the mechanism has yet to befurther Study, and we look forward to allergic rhinitis to find ways to prevent early.