Increases in airway eosinophilia and a th1 cytokine during the chronic asymptomatic phase of asthma

Abstract

Background: Studies using allergen challenge models have suggested Th2 cytokines promote airway inflammation in asthma. We assessed mediators of airway inflammation during the chronic asymptomatic phase of asthma.

Methods: Nine non-atopic asthma (NAA) patients, 19 atopic asthma (AA) patients, 20 atopic controls (AC), and 38 normal controls (NC) underwent sputum induction while asymptomatic. Sputum total cell counts and differentials were determined; levels of cytokines IL-4, IL-5, IL-13, GM-CSF, and IFN-gamma, and chemokines eotaxin (CCL11) and RANTES (CCL5) were measured by ELISA; and levels of eosinophil-derived neurotoxin (EDN) were measured by radioimmunoassay.

Results: NAA patients showed higher % eosinophils and total eosinophils compared to AA. NAA and AA patients showed higher IFN-gamma and EDN levels compared to AC and NC, with no differences in IL-4, IL-5, or IL-13 levels among the four groups. GM-CSF levels were higher in AA patients compared to AC or NC. In NAA, AA, and AC patients, % eosinophils and EDN levels correlated positively with IFN-gamma, GM-CSF, eotaxin, and RANTES, but not with IL-5 levels.

Conclusions: Baseline airway inflammation of intrinsic and extrinsic asthma is characterized by eosinophilic inflammation and the Th1 cytokine, IFN-gamma. GM-CSF, instead of IL-5, and chemokines may coordinate airway eosinophilia during the chronic asymptomatic phase of asthma.

Figure 1

Absolute numbers of sputum eosinophils (Fig. 1-A) and sputum EDN (Fig. 1-B) levels from the four groups. Levels are expressed as box and whisker plots with range and values displayed. Dot lines represent the sensitivity levels of the EDN assay.

Figure 2

Comparisons of sputum cytokines GM-CSF (2-A) and IFN-γ (Fig. 2-B) levels in the 4 groups, including IFN-γ/IL-5 (Fig. 2-C) and IFN-γ/IL-13 (Fig. 2-D) ratios. Levels are expressed as box and whisker plots with range and values displayed. Dot lines represent the sensitivity levels of the assay.

Figure 3

Comparisons of sputum eotaxin (Fig. 3-A) and RANTES (Fig. 3-B) levels in the 4 groups. Levels are expressed as box and whisker plots with range and values displayed. Dot lines represent sensitivity levels of the assay.