| Autor: |
Brieland, Joan K., Jackson, Craig, Menzel, Fred, Loebenberg, David, Cacciapuoti, Anthony, Halpern, Judy, Hurst, Stephen, Muchamuel, Tony, Debets, Reno, Kastelein, Rob, Churakova, Tatyana, Abrams, John, Hare, Roberta, O'Garra, Anne |
| Zdroj: |
Infection and Immunity; March 2001, Vol. 69 Issue: 3 p1554-1560, 7p |
| Abstrakt: |
ABSTRACTCytokine networking in the lung in response to inhaledAspergillus fumigatuswas assessed using a murine model of primary pulmonary aspergillosis in immunocompetent Crl:CF-1 mice. Inhalation of virulent A. fumigatus(6 × 106CFU) resulted in the induction of interleukin 18 (IL-18), tumor necrosis factor alpha (TNF-α), IL-12, and gamma interferon (IFN-γ) protein in bronchoalveolar lavage fluid and/or lung tissue. Induction of immunoreactive IL-18 preceded induction of TNF-α protein, which preceded induction of immunoreactive IL-12 and IFN-γ. Real-time reverse transcriptase (RT) PCR analysis of infected lung tissue demonstrated that induction of IL-18 protein also preceded induction of pulmonary TNF-α, IL-12, and IFN-γ mRNAs. Mice were subsequently treated with cytokine-specific neutralizing monoclonal antibodies (MAbs) to the IL-18 receptor (anti-IL-18R MAb), TNF-α (anti-TNF-α MAb), IL-12 (anti-IL-12 MAb), and/or IFN-γ (anti-IFN-γ MAb), and effects on intrapulmonary cytokine activity and growth of A. fumigatuswere assessed in infected lung homogenates. Simultaneous neutralization of IL-12 and IL-18 resulted in decreased levels of immunoreactive TNF-α, while neutralization of IL-18, TNF-α, or IL-12 alone or of IL-18 and IL-12 together resulted in decreased levels of immunoreactive IFN-γ. Simultaneous neutralization of IL-12 and IL-18 or neutralization of TNF-α alone or in combination with IL-12, IL-18, or IFN-γ also resulted in a significant increase inA. fumigatusCFU in lung tissue. Taken together, these results demonstrate that endogenous IL-18, IL-12, and TNF-α, through their modulatory effects on both intrapulmonary cytokine activity and growth of A. fumigatus, play key roles in host defense against primary pulmonary aspergillosis. |
| Databáze: |
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