Am. J. Respir. Crit. Care Med., Volume 164, Number 1, July 2001, 109-116

Exacerbations of Bronchitis
Bronchial Eosinophilia and Gene Expression for Interleukin-4, Interleukin-5, and Eosinophil Chemoattractants

JIE ZHU, YU SHENG QIU, SWATI MAJUMDAR, ELIZABETH GAMBLE, DEAN MATIN, GRAZIELLA TURATO, LEONARDO M. FABBRI, NEIL BARNES, MARINA SAETTA, and PETER K. JEFFERY

Department of Gene Therapy, National Heart and Lung Institute, Imperial College School of Medicine at the Royal Brompton Hospital, and London Chest Hospital, London, United Kingdom; and Institute of Occupational Medicine, University of Padua, Padua, Italy

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 probably responsible for the tissue eosinophilia in bronchial biopsies obtained from three groups of nonatopic subjects: (1) healthy nonsmokers (n = 7; FEV₁ % predicted = 108 ± 4 [mean ± SEM]); (2) nonasthmatic smokers with chronic bronchitis (CB) in a stable phase of their disease (n = 11; FEV₁ % predicted: 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 count eosinophils. We performed in situ hybridization to visualize and enumerate cells expressing the genes for interleukin (IL)-4 and IL-5 and the eosinophil chemokines eotaxin, monocyte chemoattractant protein (MCP)-4, or regulated on activation, normal T-cell expressed and secreted (RANTES). We confirmed an increase in EG2-positive eosinophils in patients with CB in exacerbation. We found messenger RNA (mRNA) positivity for IL-4 and IL-5 in CB, but the between-group differences were not statistically significant. However, the numbers of lymphomononuclear cells expressing eotaxin mRNA were significantly greater in the smokers with CB than in the healthy nonsmokers without CB (p < 0.01). Following an exacerbation, RANTES expression was upregulated and this chemokine was strongly expressed in both the surface epithelium and in subepithelial lymphomononuclear cells: only RANTES showed a significant positive correlation with the increasing number of EG2-positive cells (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 and subepithelium most likely accounts for the increased eosinophilia associated with an exacerbation of bronchitis.

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