Background: Five to twenty percent of healthy, nonasthmatic individuals exhibit airway hyperreactivity. Because cytokines are important intermediates in airway responses, we investigated the relationship between serum cytokines and airway responsiveness in a well-characterized population of pregnant women. Methods: We analyzed serum levels of interleukin-4 (IL-4), IL-5, IL-6, interferon-γ (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in frozen sera from 240 pregnant nonasthmatic subjects from a previous study of airway responsiveness and preterm labor for their relationship to methacholine challenge test results. Results: Serum IFN-γ and GM-CSF levels were significantly related to levels of methacholine airway responsiveness among nonasthmatics in this population. Nonasthmatics with PD20 <8 µmol (the highest level of airway responsiveness) had the highest mean serum levels of IFN-γ and GM-CSF, those with 8 ≤ PD20 ≤ 50 µmol had intermediate levels, and those with PD20 >50 µmol had the lowest levels. Both serum IFN-γ and GM-CSF levels were also significantly related to the log dose-response slope for methacholine responsiveness. These relationships were confirmed in a multiple linear regression analysis controlling for age, ethnic background, and cigarette smoking. Current smoking was uniformly associated with decreased cytokine levels. Conclusion: IFN-γ, GM-CSF, and other cytokines may be useful serum markers in population studies of airway responsiveness.

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