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Hygiene Hypothesis of Asthma*: A Murine Asthma Model With Mycoplasma pneumoniae Infection FREE TO VIEW

Hong Wei Chu, MD; Joyce M. Honour, BS; Catherine A. Rawlinson, BS; Ronald J. Harbeck, PhD; Richard J. Martin, MD, FCCP
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*From the National Jewish Medical and Research Center, Denver, CO.

Correspondence to: Richard J. Martin, MD, FCCP, National Jewish Medical and Research Center, 1400 Jackson St, Denver, CO 80206

Chest. 2003;123(3_suppl):390S. doi:10.1378/chest.123.3_suppl.390S
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Airway Mycoplasma pneumoniae infection may be associated with asthma pathophysiology. However, the direct effects of M pneumoniae infection on asthma remain unknown. Using a murine allergic asthma model, we evaluated the effects of the different timing of airway M pneumoniae infection on bronchial hyperresponsiveness (BHR), lung inflammation, and the protein levels of T helper (Th) type 1 cytokines (ie, interferon [IFN]-γ), and Th2 cytokines (ie, interleukin [IL]-4) in BAL fluid. When M pneumoniae infection was administered 3 days before the allergen sensitization and challenge, the infection reduced the BHR and inflammatory cell influx into the lung. This was accompanied by a significant induction of Th1 responses. The mean (± SEM) IFN-γ levels in the BAL fluid were increased in the infected mice (490 ± 65 pg/mL) compared with those of the control mice (341 ± 36 pg/mL; p = 0.047). The mean IL-4 levels in the BAL fluid were reduced in the infected mice (41 ± 10 vs 212 ± 87 pg/mL, respectively; p = 0.056). The IFN-γ/IL-4 ratio was significantly higher in the infected mice (16.9 ± 5.6 vs 6.8 ± 2.2, respectively; p = 0.04). Contrary to this, when M pneumoniae infection was administered 2 days after the allergen sensitization and challenge, the infection initially caused a temporary reduction of BHR at day 3 after introduction of the infection and then increased BHR, lung inflammation, and IL-4 levels between day 7 and day 21 after introduction of the infection. The IFN-γ/IL-4 ratio in the BAL fluid of infected mice was increased at day 3 and then decreased at day 7 after introduction of the infection. Our data suggested that M pneumoniae infection could modulate both physiologic and immunologic responses in the murine asthma model. Our animal models also may provide a new means with which to understand the role of infection in asthma pathogenesis and may give evidence for the asthma hygiene hypothesis.

Abbreviations: BHR = bronchial hyperresponsiveness; IFN = interferon; IL = interleukin; Th = T helper




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