| Popis: |
Rationale After Sendai virus-induced bronchiolitis as weanlings, BN, unlike F344, rats develop a postbronchiolitis asthma-like phenotype, which is prevented by IFN-γ therapy. Innate mechanisms of Sendai virus-induced IFN-γ production, which are dependent on NK cells and the production of IFN-γ-inducing cytokines (IL-12 and IL-18), are markedly attenuated in BN, compared with F344, weanlings. GM-CSF and Flt-3 ligand may enhance innate immunity by augmenting dendritic cell or dendritic and NK cell development, respectively. We hypothesized that treatment with GM-CSF and Flt-3 ligand would counteract the reduced capacity of BN weanlings to secrete IFN-γ and IFN-γ-inducing cytokines in response to virus. Methods Splenocytes from uninfected weanlings were preincubated for 16 h with or without GM-CSF or Flt-3 ligand and then for 24 h with or without Sendai virus. IFN-γ, IL-12, and IL-18 were measured in supernates by ELISA. Results GM-CSF and Flt-3 ligand triggered 12- and 8-fold increases, respectively, in virus-induced IFN-γ production by BN splenocytes ( p Conclusions GM-CSF-mediated enhancement of virus-induced IFN-γ production from BN splenocytes appeared to result from increases in IL-12 secretion, suggesting that GM-CSF augmented deficient dendritic cell activity. Flt-3 ligand-mediated, IL-12-independent increases in virus-induced IFN-γ production may arise from enhancement of deficient NK cell responses. These results suggest a basis for attenuated innate anti-viral responses in BN weanlings. |
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