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Prior airway exposure to allergen increases virus-induced airway hyperresponsiveness  Mika J Mäkelä, MD, Ralph Tripp, PhD, Azzeddine Dakhama, PhD, Jun-Won.

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Presentation on theme: "Prior airway exposure to allergen increases virus-induced airway hyperresponsiveness  Mika J Mäkelä, MD, Ralph Tripp, PhD, Azzeddine Dakhama, PhD, Jun-Won."— Presentation transcript:

1 Prior airway exposure to allergen increases virus-induced airway hyperresponsiveness 
Mika J Mäkelä, MD, Ralph Tripp, PhD, Azzeddine Dakhama, PhD, Jun-Won Park, MD, Toshihide Ikemura, PhD, Anthony Joetham, BSc, Matti Waris, PhD, Larry J Anderson, MD  Journal of Allergy and Clinical Immunology  Volume 112, Issue 5, Pages (November 2003) DOI: /S (03)

2 FIG 1 RSV-induced airway responsiveness to inhaled MCh is enhanced by prior allergen airway exposure. BALB/c mice were exposed to aerosolized OVA or PBS exclusively through the airways for 30 minutes daily on 10 consecutive days. On day 11, mice were either sham-inoculated or RSV-infected. Airway responsiveness to inhaled MCh was assessed on day 6 after RSV infection by barometric whole-body plethysmography. Data are expressed as percentage of baseline Penh values obtained after inhaled PBS challenge. PBS-sham, PBS-exposed; sham-inoculated, OVA-sham; OVA-exposed, sham-inoculated; PBS-RSV, PBS-exposed; RSV-infected, OVA-RSV; OVA-exposed, RSV-infected. There were no significant differences in baseline Penh values among groups. ∗Significantly different from PBS-sham; #significantly different from all other groups (P < .05). NS, Not significant. Journal of Allergy and Clinical Immunology  , DOI: ( /S (03) )

3 FIG 2 BAL cell composition. Same groups of mice as in Fig 1. ∗Significant differences compared with PBS-sham or OVA-sham (P < .05, ANOVA with Fisher PLSD tests for multiple comparisons). Journal of Allergy and Clinical Immunology  , DOI: ( /S (03) )

4 FIG 3 Lung histopathology. Formalin-fixed, paraffin-embedded lung tissue sections were stained with PAS reaction to detect mucus-producing goblet cells. Abbreviations as in Fig 1. Prior airway exposure to OVA increased RSV-induced airway tissue inflammation and markedly enhanced mucus production in central intrapulmonary airways (arrowheads). Journal of Allergy and Clinical Immunology  , DOI: ( /S (03) )

5 FIG 4 Frequency of TH1 and TH2 cytokine-producing T cells in the lung. Cytokine-producing T cells were detected in the lung digests obtained on day 4 (A) and day 7 (B) after infection by double immunostaining for surface expression of CD3 and intracellular expression of IL-4, IL-5, IL-12, or IFN-γ without restimulation of cells in vitro. ∗Significantly different from PBS group; #significantly different from all the other groups (P < .05, Kruskal-Wallis test). Journal of Allergy and Clinical Immunology  , DOI: ( /S (03) )

6 FIG 4 Frequency of TH1 and TH2 cytokine-producing T cells in the lung. Cytokine-producing T cells were detected in the lung digests obtained on day 4 (A) and day 7 (B) after infection by double immunostaining for surface expression of CD3 and intracellular expression of IL-4, IL-5, IL-12, or IFN-γ without restimulation of cells in vitro. ∗Significantly different from PBS group; #significantly different from all the other groups (P < .05, Kruskal-Wallis test). Journal of Allergy and Clinical Immunology  , DOI: ( /S (03) )

7 FIG 5 Ratio of TH1 to TH2 cytokine-expressing lung T cells. Data (mean ± SEM) reflect normalized ratio of IFN-γ to IL-4 cytokine-producing T-cell frequencies in the lung. Normalized ratio was obtained by using the formula [(frequency of IFN-γ + T cells/ frequency of IL-4+ T cells)−1], where 1 corresponds to equal frequencies for both cell populations. ∗Significantly different from PBS group; #significantly different from all the other groups (P < .05, ANOVA with Fisher PLSD tests for multiple comparisons). Journal of Allergy and Clinical Immunology  , DOI: ( /S (03) )

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