Serum Cytokine Levels, Cigarette Smoking and Airway Responsiveness among Pregnant Women

Abstract

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-gamma (IFN-gamma), 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-gamma and GM-CSF levels were significantly related to levels of methacholine airway responsiveness among nonasthmatics in this population. Nonasthmatics with PD(20) <8 micromol (the highest level of airway responsiveness) had the highest mean serum levels of IFN-gamma and GM-CSF, those with 8 <or= PD(20) <or= >50 micromol had intermediate levels, and those with PD(20) >>50 mol had the lowest levels. Both serum IFN-gamma 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-gamma, GM-CSF, and other cytokines may be useful serum markers in population studies of airway responsiveness.