| Asthma is a chronic disease characterized by reversible airway obstruction, pulmonary inflammation and airway remodel. Eosinophils (EOS) is the key effector cells of asthma, which can produce many inflammatory mediators, such as eosinophilic cationic protein (ECP), leukotriene and so on. The increased number of EOS in serum is associated with asthma exacerbation. IL-5 and IL-13 are cytokines which mainly produced by Th2 cells. IL-5 regulates multiple major EOS functions, including cellular proliferation, mobilization from the bone marrow into the peripheral circulation, maturation, activation,tissue recruitment, survival,and priming to stimulating agents. IL-13exhibits stimulatory activity to multiple cell types that are involved in asthma, including B cells, mast cells, EOS, pulmonary epithelial cells, fibroblasts and airway smooth muscle cells. In addition, IL-13 can also stimulate airway epithelial cells to produce Eotaxin which can increase the number of EOS in lung. IL-5 receptor (Interleukin-5 receptor , IL-5R ) can specifically bind to IL5. Soluble IL-5 receptor (sIL-5R ) which is potential anti-inflammatory can suppress the activation of EOS and basophils in vitro. IL-13 receptor 2 (IL-13R 2) is called as a "decoy"receptor. It can down regulate the level of IL-13.There are three forms of IL-13R 2: membrane-binding form, intracellular form and extracellular soluble form. Soluble IL-13R 2 (sIL-13R 2) plays a key role in response to IL-13. This study investigated the effects of the combination of sIL-5R and sIL-13R 2 on asthmatic eosinophilic airway inflammation and airway hyperresponsiveness (AHR), so as to provide a new method for the treatment of asthma.Objective: To investigate the potential therapeutic value of soluble interleukin 5 receptor (sIL-5R ) combined soluble interleukin 13 receptor 2(sIL-13R 2) in asthma by observing the effect of the combination on airway inflammatory response and the airway hyperresponsiveness in sensitized mice.Methods:The 40 BLAB/c mice were devided randomly into five groups: control group (group A), asthmatic group (group B) ,sIL-5R group(group C), sIL-13R 2group (group D) and sIL-5R +sIL-13R 2 group (group E). Except group A, mice in other groups were sensitized and challenged with ovalbumin (OVA) to establish asthmatic models, while mice in group A were treated with saline instead of OVA. Mice in group C were injected intraperitoneally with sIL-5R (100μg), 30min before challenged. Mice in group D or E were given sIL-13R 2(100μg) or sIL-5R (100μg)+sIL-13R 2(100μg) in the same way as group B, while mice in group A and group B received saline. Evaluate the BALF cell counts. Histological examinations were undertaken. The airway resistance stimulated by different doses of methacholine chloride was analyzed.Results:①Total cell and eosinophil number of BALF were all increased considerably after OVA challenge (P<0.01,P<0.01). The infection of lung issue was significant. After the intervention of sIL-5R ,sIL-13R 2 and a combination of sIL-5R and sIL-13R 2,both total cells and the EOS were decreased in BALF(respectively P < 0.01).Compare to the intervention of sIL-5R or sIL-13R 2 ,the intervention of a combination of sIL-5R and sIL-13R 2,both total cells and EOS were more decreased (respectively P<0.01).Inflammatory infiltration of lung tissue lightened obviously in the last three groups, and the sIL-5R +sIL-13R 2 group was more lighter than the other two.②Compared with control group, airway resistance of asthmatic group stimulated by methacholine chloride was highe(rP<0.01).There was no difference between asthmatic group and sIL-5R group(P>0.05).Airway resistance to methacholine chloride was decreased significantly in sIL-13R 2 group and sIL-5R +sIL-13R 2 group(P<0.01, P<0.01). Compared with sIL-13R 2 group, the airway resistance of sIL-5R +sIL-13R 2 group was more decreased (P<0.01).Conclusion: SIL-5R combined sIL-13R 2 could significantly alleviate airway inflammation and AHR of the asthmic mice. |
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