Immunotherapeutic Effects Of CpG ODNs In Murine Models Of RSV-induced Asthma And OVA-induced Asthma.

Introduction : Allergic asthma is an inflammatory disease of theairways which involves the role of many cells in particular mast cells,eosinophils, basophils,macrophages and T lymphocytes and their productswhose activation not only orchestrates increased T helper cell, type2 (Th2)-like inflammatory response against the T helper, type 1 (Th1)anti-inflammatory immune response but also progressively manifests asairway inflammation and hyper responsiveness. Present understanding of allergic diseases, including asthma,suggeststhat their pathogenesis is due to strong Th2 immune response againstotherwise benign specific antigens (allergens) and that immunotherapy is arelatively uncommon alternative treatment for allergic diseases type 2T-helper-cell (Th2) immune responses mediated by the increased secretionof IL-4, IL-5, IL-9, IL-13, granulocyte-macrophage colony-stimulatingfactor (GM-CSF),and mastocytosis other inflammatory infiltrates increasedlevels of CD4+cells, IgE are key in the pathogenesis of allergic immunedisorders, including allergen-induced asthma. At present, the most widelyused anti allergy treatments are corticosteroid. Although steroids are oftensuccessful in minimizing the manifestations of airway inflammation andhyper responsiveness, their use is not disease modifying or curative, andchronic therapy is needed to prevent pathological progression of asthma. 5 Previous Studies have demonstrated the ability of CpG-ODNs ineffecting the deviation of established Th2 immune responses to T helper,type 1 (Th1) anti-inflammatory immune response, besides regulatingexcessive Th1 bias, and henceforth serving as a homeostatic mechanism forthe Th1-Th2 balance. At the molecular level, CpG ODNs modify theTh1/Th2 cellular balance by inducing type 1 T-helper-cell (Th1) responsescharacterized by the modulated secretion of regulatory cytokines such asIL-12 IL-10, tumor growth factor (TGF)-β and immunosuppressivecytokines like Interferon (IFN)-γ from NK cells, a process which is highlydependent on macrophage-derived IL-12 to reverse, and/or suppress theinfluence of type 2 T-helper-cell (Th2) allergic inflammatory responsecharacteristic of asthma. Whereas, recent studies have demonstrated CpG-ODNs' ability toprevent the development of eosinophilic airway inflammation andbronchial hyper reactivity in a murine model of OVA induced asthma, wewere interested in comparing the efficacy of CpG ODNs monotherapy withthat of systemic corticosteroids monotherapy in two murine models ofacute exacerbation of RSV-induced asthma and OVA-induced asthma. Objective: Henceforth, this experimental study, was designed toinvestigate, evaluate and compare the immunomodulating effects ofCpG-ODNs and Dexamethasone on eosinophilic inflammation, airwayhyper responsiveness (AHR) and peribronchial eosinophil clearance in twomodel groups of BALB/c mice respectively sensitized to and challengedwith ovalbumin (OVA) and respiratory syncytial virus (RSV) inactivatedby ultraviolet radiation. Method: The two asthma model groups, the OVA group and the RSVgroup each of 30 female BALB/c mice were established and each groupsubdivided into three sub groups of 10 mice each, namely the Asthmanon-treated group (Asthma Control group), CpG-ODN treated mice(CpG-group) and the Dexamethasone treated (DEX group). Each mice inthe OVA subgroups and RSV subgroups were intraperitoneally inoculatedonce a week, four times with OVA and RSV respectively prior tointraperitoneal administration of either normal saline (N.S), CpG ODNs orDexamethasone (DEX) monotherapies daily, twice before and after theintranasal challenge by OVA and RSV respectively done twice intermittentover a period of one month till mice sacrifice. Whole blood was collectedby retro bulbar puncture with anti-coagulant EDTA filled capillary tubefrom each OVA sensitized mice and RSV sensitized mice 24 hours and 48hours after final allergen challenge respectively and then assessed by Flowcytometry for peripheral blood T lymphocyte subset percentage of CD3+Tcells,CD4+T cells, and the CD4+/CD8+ratio. Blood seru...