| Summary: | <p>Abstract</p> <p>Background</p> <p>Previously, we demonstrated that OVA-loaded macrophages (OVA-Mφ) partially suppress OVA-induced airway manifestations of asthma in BALB/c mice. <it>In vitro </it>studies showed that OVA-Mφ start to produce IL-10 upon interaction with allergen-specific T cells, which might mediate their immunosuppressive effects. Herein, we examined whether IL-10 is essential for the immunosuppressive effects of OVA-Mφ <it>in vivo</it>, and whether <it>ex vivo </it>stimulation of the IL-10 production by OVA-Mφ could enhance these effects.</p> <p>Methods</p> <p>Peritoneal Mφ were loaded with OVA and stimulated with LPS or immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) <it>in vitro</it>. The increase of IL-10 production was examined and, subsequently, <it>ex vivo </it>stimulated OVA-Mφ were used to treat (i.v.) OVA-sensitized mice. To further explore whether Mφ-derived IL-10 mediates the immunosuppressive effects, Mφ isolated from IL-10<sup>-/- </sup>mice were used for treatment.</p> <p>Results</p> <p>We found that stimulation with LPS or ISS-ODN highly increased the IL-10 production by OVA-Mφ (2.5-fold and 4.5-fold increase, respectively). ISS-ODN stimulation of OVA-Mφ significantly potentiated the suppressive effects on allergic airway inflammation. Compared to sham-treatment, ISS-ODN-stimulated OVA-Mφ suppressed the airway eosinophilia by 85% (vs. 30% by unstimulated OVA-Mφ), IL-5 levels in bronchoalveolar lavage fluid by 80% (vs. 50%) and serum OVA-specific IgE levels by 60% (vs. 30%). Importantly, IL-10<sup>-/-</sup>Mφ that were loaded with OVA and stimulated with ISS-ODN <it>ex vivo</it>, failed to suppress OVA-induced airway inflammation.</p> <p>Conclusions</p> <p>These results demonstrate that Mφ-derived IL-10 mediates anti-inflammatory responses in a mouse model of allergic asthma, which both can be potentiated by stimulation with ISS-ODN.</p>
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