Role Of Interleukin 18 In The Recruitment Of Eosinophils Into The Lung Of OVA-sensitized Mice

PrefaceTwo types of T helper (Th) cells - Th1 and Th2 cells played different roles in immune response and immunopathology .The polarization of the balance of Thl/Th2 response resulted in the major of immunopathology of lung in asthma patients. Th2 response improved asthma, but Th1 response decreasesd the risk of allergy. Proliferated eosinophils recruited into the trachea which led to inflammation in airway. Thus, regulating the balance of Th1/Th2 response become to be critical in asthma therapy.Interleukin-18 was a member of the interleukin-1 family of cytokines, which potently inducesd IFN-gamma, was found recently. Most of studies demonstrated that IL-18 could decline the increased airway hyperreactivity, and play an important role in regulating eosinophil recruitment into respiratory tract. However, recently studies reported that IL-18 has multi bioactivities in stimulating both Th1 and Th2 responses.Kodama reported that IL-18 enhanced eosinophil recruitment into the trachea in IL-18 gene knockout mice. He showed that IL-18 has a role in induction and maintain the immune response occurred at the epithelium of respiratory tract. He also discussed that IL-18 induced local proliferation of T cells in lung of IL-18 gene knockout mice after administration of recombinant murine IL-18 intraperitoneally. They found the number of eosinophil cells in lung of IL-18 gene knockout mice showed a higher number than that in lung of wide-type control mice.However, Kumano reported that the administration of recombinant murine IL-18 enhanced antigen-induced eosinophil recruitment into the trachea and bronchoalveolar lavage fluid (BALF) of sensitized mice in a dose-dependent manner. That was, IL-18 , by it self, may contribute to the development and exacerbation of airway inflammation in asthma. Linpei compared the IL-18 level in BALF between asthmatic, sarcoidosis and health people. He found that there has a relationship between IL-18 level and the airway inflammatory in asthma.Interleukin 18 binding protein (IL-18BP) was a new number of immunoglobulin super-family, which was glucoprotein. IL-18BP inhibits bioactivities of IL-18 by preventing Th1 -induced IFN-γproduction and downregulating the activity of NF-κB. We copied mouse asthma model to determine whether eosinophils recruitment could be reduced by reducing IL-18 level in peripheral blood.Thus, we suggest that IL-18 may associate with the airway inflammatory in OVA-sensitized mice.Materials and MethodsSix- wk-old female BALB/c mice were divided into three groups, (a) saline control group, (b) OVA-sensitized asthma group and (c) IL-18BP-treated group. In each group 8 mice was used in this experiment. Mice of group b and group c were administered 10μg of OVA and 20μg of aluminium hydroxide on days 1 and 8, then challenged with 5% OVA for 20 minutes on day 21-26. Mice were sacrificed 24 hour after the last antigen challenge. Saline control group was administrated with saline only. In IL-18BP treatment groups, mice received 5μg of IL-18 binding protein in conjunction with OVA on days 17,18,19,20 and 21 intraperitoneally. Serum and BALF of mice in each group were collected. IL-18 level in serum was detected by ELISA. The number of cells and the percentage of eosinophil in BALF were counted.ResultsIL-18 serum level in IL-18 BP-treated group was significantly decreased compared with that in OVA-sensitized asthma mice (p<0.05). In IL-18BP-treated group, as well as in OVA-sensitized asthma group, the number of lymphocytes and the percentage of eosinophil cells in BALF exhibited a higher number than those in saline control group (p <0.01) . But no significance was observed between IL-18BP-treated group and OVA-sensitized asthma group (p >0.05). DiscussionMouse has become to be a major experimental animal for asthma study. Here, we improved the method using by Liu Chuntao in this study. Serum IL-18 level in IL-18 BP-treated group was decreased comparing with that in OVA-sensitized asthma mice. This result showed that IL-18BP bound with IL-18 partly, which did not inhibit IL-18 completely.In this study, eosinophils recruitment did not reduce by administrating IL-18 binding protein. It could be explained that IL-4, which induced by sensitization with OVA , may result in the recruitment of eosinophil cells into lung. It also could be explained that eosinophils may be mainly regulated by other cytokines, for example, IL-5, IL-13 and Eotaxin, rather than IL-18.ConclusionIL-18 may play a role in the recruitment of eosinophils into the lung of OVA-sensitized mice.