Exacerbations of bronchitis - Bronchial eosinophilia and gene expression for interleukin-4, interleukin-5, and eosinophil chemoattractants

Eosinophilia has been reported during exacerbations of bronchitis, but the mechanisms of tissue recruitment of eosinophils are unclear. We quantified eosinophils and the concurrent expression of cytokines and chemokines proba bly responsible for the tissue eosinophilia in bronchial biopsies obtained from three groups of non-atopic subjects: (1) healthy nonsmokers (n = 7; FE V1 % predicted 108 +/- 4 [mean +/- SEM]); (2) nonasthmatic smokers with chr onic bronchitis (CB) in a stable phase of their disease (n = 11; FEV1 % pre dicted: 75 +/- 5); and (3) nonasthmatic subjects with CB who sought medical advice for an exacerbation of their condition (n = 9; FEV1 % predicted: 61 +/- 8). We applied anti-EG2 antibody and immunostaining to detect and coun t eosinophils. We performed in situ hybridization to visualize and enumerat e cells expressing the genes for interleukin (IL)-4 and IL-5 and the eosino phil chemokines eotaxin, monocyte chemoattractant protein (MCP)-4, or regul ated on activation, normal T-cell expressed and secreted (RANTES). We confi rmed an increase in EG2-positive eosinophils in patients with CB in exacerb ation. We found messenger RNA (mRNA) positivity for IL-4 and IL-5 in CB, bu t the between-group differences were not statistically significant. However , the numbers of lymphomononuclear cells expressing eotaxin mRNA were signi ficantly greater in the smokers with CB than in the healthy nonsmokers with out CB (p < 0.01). Following an exacerbation, RANTES expression was upregul ated and this chemokine was strongly expressed in both the surface epitheli um and in subepithelial lymphomononuclear cells: only RANTES showed a signi ficant positive correlation with the increasing number of EG2-positive cell s (r = 0.51; p < 0.03). In conclusion, an allergic profile of inflammation can also occur in CB: the marked upregulation of RANTES in the epithelium a nd subepithelium most likely accounts for the increased eosinophilia associ ated with an exacerbation of bronchitis.