Human Cytotoxic T Lymphocyte-associated Antigen 4-immunoglobulin Fusion Protein Inhibits Airway Inflammation and Hyperresponsiveness in a Murine Model of Asthma

Abstract

BACKGROUND: CD4+ T helper cells which differentiate into the Th2 cells are crucial for the initiation and progression of allergic asthma. Human Cytotoxic T Lymphocyte- associated Antigen 4-immunoglobulin (CTLA4-Ig) has been widely used in order to block T-cell costimulation in an array of experimental animal models of T-cell-mediated diseases.
OBJECTIVE
To evaluate whether human CTLA4-Ig fusion protein inhibits airway inflammation in a murine model of OVA-induced asthma. METHOD: Six-weeks-old BALB/c mice were used and airway inflammation was induced by OVA. Human CTLA4-Ig fusion protein was administered intravenously before and after sensitization with OVA. Airway responsiveness to methacholine was measured after antigen challenge. Total IgE, OVA-specific IgE, IgG1 and IgG2a in serum samples were assessed by ELISA. Bronchoalveolar lavage (BAL) and lung section were also performed. RESULT: In mice which were treated with the human CTLA4-Ig fusion protein before and after sensitization with OVA, airway hyperresponsiveness and eosinophil count of BAL were markedly decreased. In mice which were treated with human CTLA4-Ig before sensitization with OVA, serum total IgE level were more significantly reduced than that of positive control mice. Peribronchial inflammatory cell infiltration was desreased by the treatment of human CTLA4-Ig before and after sensitization with OVA.
CONCLUSION
These results suggest that human CTLA4-Ig fusion protein may inhibit eosinophilic airway inflammation and airway hyperresponsivness in OVA-sensitized and airway challenged mice.

Human Cytotoxic T Lymphocyte-associated Antigen 4-immunoglobulin Fusion Protein Inhibits Airway Inflammation and Hyperresponsiveness in a Murine Model of Asthma

Abstract

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