Background
Anti‐tumor necrosis factor (TNF)‐α therapeutics has the potential to alleviate allergic inflammation. However, in previous studies, the systemic administration of anti‐TNF‐α agents was frequently accompanied by many adverse effects, such as infection, immunogenicity and malignancy. Efforts are made in the present study to evaluate whether or not local administration of TNF‐α antisense oligonucleotide would inhibit allergic airway inflammation and influence systemic immune responses in an ovalbumin‐induced asthmatic murine model.
Methods
The treatment effects of TNF‐α antisense oligonucleotide on mice, as well as the alternative proportion of regulatory T cells and TH2 cells, were examined and compared with untreated mice.
Results
Local administration of TNF‐α antisense oligonucleotide resulted in significantly inhibited TNF‐α expression, remarkably decreased inflammatory cell infiltration and dramatically reduced mucus hypersecretion. These treatment effects were associated with induced CD4+CD25+Foxp3+ regulatory T cells, reduced TH2 cells and generally decreased TH2‐type cytokines expression in bronchoalveolar lavage fluid. Systemic immunosuppression was not triggered by local antisense oligonucleotide administration because the proportion of CD4+CD25+Foxp3+ regulatory T cells in the blood, thymus or spleen was not affected. Attenuated 4‐1BBL expression was likely involved in the alternative proportion of T cells.
Conclusions
These findings demonstrate that local administration of TNF‐α antisense oligonucleotide contributes to anti‐inflammatory action via the enhancement of regulatory T cells‐mediated immune tolerance, which is not accompanied by systemic immunosuppression associated with systemically‐induced regulatory T cells. Copyright © 2012 John Wiley & Sons, Ltd.