Inhibition of IL-13 by antisense oligonucleotide changes immunoglobulin isotype profile in cultured B-lymphocytes

ABSTRACT

The link between IL-13 and bronchial hyper-responsiveness has brought this cytokine as a potential therapeutic target for asthma and allergic diseases. At the present study, we address the role of B cell derived IL-13 in the IgE and other immunoglobulin development. Antisense oligo for human IL-13 m-RNA was used to study IgE down regulation. Human B-lymphocytes were purified by positive selection using magnetic cell sorting and were cultured in the complete medium plus anti-CD40 monoclonal antibody and recombinant human IL-4. Immunoglobulin assay was performed by ELISA in the presence and absence of antisense oligonucleotide. We demonstrated that IL-13 antisense causes the decrease of IgE and increase of IgA significantly and no significant changes in IgM and IgG levels [p<0.01]. We also demonstrated that both IL-13 inhibition and IL-4 removal cause the complete blocking of IgE and significant decrease of IgM and IgG levels. Our IL-13 antisense oligo can block B-cell IL-13 productions and consequently inhibits IgE production followed by IgA class switching in vitro. We suggest that in contrast to the IL-4, IL-13 is apparently more potent in the IgE switching and has no significant role in IgG and IgM levels