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(Chest. 2003;123:390S.)
© 2003 American College of Chest Physicians

Hygiene Hypothesis of Asthma*

A Murine Asthma Model With Mycoplasma pneumoniae Infection

Hong Wei Chu, MD; Joyce M. Honour, BS; Catherine A. Rawlinson, BS; Ronald J. Harbeck, PhD and Richard J. Martin, MD, FCCP

* 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

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]-{gamma}), 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-{gamma} 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-{gamma}/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-{gamma}/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.


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





This Article
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Right arrow Articles by Martin, R. J.

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