| With the incidence of allergic rhinitis increasing around the world,it is imperative to find better treatment modalities, Eosinophils, mastcells and Th2 cells that are effector cells play key roles in thepathogenesis of allergic rhinitis. These effector cells with CCR3(CCChemokine receptor 3)will migrate into tissues with chemokins' bindingCCR3.Interaction of CCR3 and its agonist perform proallergenicfunctions including effector cells activation and amplification of Th2responses and inflammatory mediator release as well as inflammatory cellrecruitment. Eotaxin locally mediates the migration of eosinophils intotissues which can merely bind CCR3. CC Chemokines signal theses effectorcells through a kind of G protein-coupled seven transmembranereceptors (CCR3). The unexpected complexity of the chemokine systemappears to allow for the precise control of leukocyte trafficking invivo, which fine-tunes the immune response. The distinct activity ofchemokines and the unique pattern of chemokine receptor expression ondefined leukocyte subsets have afforded an opportunity to manipulatethe immune system in a more defined manner. It has been demonstratedthat Anti-CCR3 monoclonal antibody can inhibit CCR3 in vitro. Inconclusion, It is feasible to treat allergic rhinitis with CCR3antagonist in theory. To date, several pharmaceutical approaches havebeen described, including amonoclonal antibodies, amino terminusmodification of natural chemokines and small molecular compounds. Wechoice SB328437(C21H18N2O5) with better bioavailabilityGlucocorticosteroid represent the most effective treatment for allergicrhinitis, which mostly inhibit the synthesis of inflammatorycytokine.However, there isn't any report on applying SB328437 invivo.Its effect and side effect remain unpredictable. Objective: To explore a new better treatment modality, study thepotential role of CCR3 antagonist SB328437 in the treatment of allergicrhinitis, compare their mechanism and effect between SB328437 anddexamethasone, analyze the relation among IgE, CCR3, IL—4mRNA, eotaxinmRNA and Allergic rhinitis.Methods: Sixty BALB/C mice were randomly divided into allergicrhinitis group, SB328437 therapy group, DXM therapy group and controlgroup. Ovalbuminwas used to sensitilize allergic rhinitis. Treatedwith SB328437 before OVA chanllenges in B group, with DXM in C group.Comparing their symptom score, the number of EOS and histologicalmorphous. Detecting the express of enhanced green fluorescence proteinscorresponding to CCR3 by immunoenzymatic technique. Determining thetotal serum IgE by avidin biotin system-enzyme linked immunosorbentassay (ABS-ELISA), Analyzing the express of IL-4mRNA and eotaxin mRNAby reverse transcription polymerase chain reaction(RT-PCR).Analyzingthe data by SPSS13.0 statistics software.Result:①symptom score: The score in A group(7.3±1.0) issignificantly higher than that in B group (1.8±0.7),C group (3.9±1.1) and D group (0.7±0.6) (p＜0.01) ; the sore in A group issignificantly lower than that in C group (p＜0.01).②The number ofeosinophils in the epithelium: EOS in A group (7.40±1.24) issignificantly more than in Bgroup (1.27±0.80),Cgroup (1.47±0.64)and D group (0.47±0.52) (p＜0.01); B group is similar to C group(p＞0.05).③histological morphous: A group: cilia defluxion,tissue dropsy, Vascular proliferation, EOS infiltration. B, C, D group:There aren't these phenomena.④The express of enhanced greenfluorescence proteins corresponding to CCR3: A group: The express isobvious,mainly located in epithelialis and endotheliocyte.B,C,Dgroup: The express is microcrystalline.⑤The total serum IgE(ng/ml):The amount in A group (116.125±10.696) is significantlylarger than that inBgroup (68.250±4.334),Cgroup (73.000±4.342)and D group (26.125±4.190) (p＜0.01);B group is similar to C group(p＞0.05).⑥The express of IL-4 mRNA (integral calculus opticaldensity): The express inA group(0.4881±0.1863) is significant higherthan that in B group (0.0778±0.0381),C group (0.1593±0.0897) and D group (0.1930±0.0049) (p＜0.01); B group is similar to C group(p＞0.05).⑦The express of eotaxin mRNA (integral calculus opticaldensity): The express in A group (0.9055±0.3624) is significant higherthan that in B group (0.2103±0.1325), C group (0.3844±0.2487)andDgroup (0.3870±0.1847) (p＜0.01);BgroupissimilartoCgroup(p＞0.05).Conclusion:①The model of allergic rhinitis has been successfullyduplicated in BALB/C mice.②The data we have detected in allergicrhinitis group, such as symptom score, the number of eosinophils in theepithelium, the express of enhanced green fluorescence proteinscorresponding to CCR3, the total serum IgE, the express of IL-4 mRNAand Eotaxin mRNA is obviously different from other groups.③BothSB328437 and dexamethasone are available in the treatment of murinemodel of allergic rhinitis.④SB328437 is more potent in allevatingsymptoms than DXM.⑤Obviously alleviating symptoms without any sideeffect, SB328437 could be a kind of new immunotherapy against allergicrhinitis. |
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