Am. J. Respir. Cell Mol. Biol., Volume 23, Number 2, August, 2000 228-233

Priming of Allergic Immune Responses by Repeated Ozone Exposure in Mice

Ulrich Neuhaus-Steinmetz, Felix Uffhausen, Udo Herz, and Harald Renz

Institute of Laboratory Medicine and Pathobiochemistry, Charité Campus Virchow Clinic, Berlin; and Department for Clinical Chemistry and Central Laboratory, Clinic of the Philipps-University Marburg, Marburg, Germany

The effects of repeated ozone exposures on the development of immune responses toward ovalbumin (OVA) were investigated in BALB/c and C57BL/6 mice. Ozone exposures (180 to 500 µg/m³; 4 h, three times/wk for 4 wk) were combined with a protocol of OVA-aerosol exposure (1% OVA). Immediate cutaneous hypersensitivity (ICHS) reactions and antibody titers were assessed in parallel to cytokine levels of bronchoalveolar lavage fluids. In BALB/c mice, ozone triggered a T-helper (Th)2-like response indicated by dose-dependent increases in total serum immunoglobulin (Ig) E (from 133 to 821 ng/ml), interleukin (IL)-4 (from 60 to 208 pg/ml), and IL-5 levels (from 43 to 356 pg/ml), and by the recruitment of eosinophils and lymphocytes into the airways. Ozone exposure (500 µg/m³) in parallel to OVA-aerosol exposure increased anti-OVA IgG₁ antibody titers by 80%, leukotrienes (C₄/D₄/E₄) by 60%, and airway responsiveness (11.3 versus 7.2 mg/ml methacholine), and doubled the frequency of positive ICHS reactions. In C57BL/6 mice, only the combination of OVA and ozone exposure induced positive ICHS reactions, doubled anti-OVA IgG₁, and suppressed anti-OVA IgG_2a (64%) antibody titers. Ozone, therefore, shifted the immune responses to OVA toward a Th2-like pattern in both "IgE-high responder" (BALB/c) and "IgE-low responder" (C57BL/6) mice.

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