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Am. J. Respir. Crit. Care Med., Volume 164, Number 6, September 2001, 1047-1052

Effects of Budesonide and Formoterol on NF-kappa B, Adhesion Molecules, and Cytokines in Asthma

SUSAN J. WILSON, ANNIKA WALLIN, GIOVANNI DELLA-CIOPPA, THOMAS SANDSTRÖM, and STEPHEN T. HOLGATE

Respiratory Cell and Molecular Biology Research Division, School of Medicine, University of Southampton, Southhampton, United Kingdom; University Hospital of Northern Sweden, Umeå, Sweden; and Novartis, Horsham Research Centre, Horsham, United Kingdom

The asthmatic inflammatory response can be attenuated by corticosteroids and in part by beta 2-agonists. We investigated if these effects are accompanied by a downregulation in nuclear factor kappa B (NF-kappa B), a transcription factor regulating many of the cytokine and adhesion molecule genes expressed in allergic inflammation. Bronchial biopsies were taken before and after 8 wk treatment with formoterol, budesonide, or placebo from atopic asthmatics. Biopsies were processed into glycol methacrylate and stained immunohistochemically for eosinophils (as an index of inflammation), activated and total NF-kappa B, adhesion molecules, and cytokines. After budesonide treatment there was a significant decrease in the number of submucosal cells staining for total NF-kappa B, granulocyte macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha ), accompanied by a significant decrease in mucosal eosinophils and expression of vascular cell adhesion molecule-1 (VCAM-1) in the endothelium and interleukin-8 (IL-8) in the epithelium. After formoterol treatment there was a significant decrease in eosinophils and the epithelial expression of activated NF-kappa B, but these changes were not accompanied by reduced immunoreactivity for adhesion molecules or cytokines. We conclude that at least some of the therapeutic efficacy of inhaled corticosteroids is mediated through inhibition of NF-kappa B-regulated gene expression, whereas the reduction in airway eosinophilia by long-acting beta 2-agonists probably operates through alternative pathways.

Keywords: budesonide; formoterol; NF-kappa B; immunohistochemistry; asthma




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