Aspects of the inflammatory response and formation of polys in the nasal and sinus mucosa

Abstract: Experimental sinusitis was induced in rabbits by ostial occlusion, with or without subsequent inoculation of Streptococcus pneumoniae, Staphylococcus aureus or Bacteroides fragilis The general inflammatory response, including goblet cell differentiation and polyp formation, was morphologically investigated. Polyps were experimentally induced by a combining mechanical trauma the mucosa with infection or by injection of agarose or N-formyl-methionyl-leucyl-phenylalanine (FMLP) into the maxillary sinus. The effect of systemic pre-treatment with betamethasone on experimentally induced polyps was studied. In order to investigate neurogenic mechanisms in the mucosal defense, rabbits were treated with topical application of capsaicin or underwent surgical denervation of the nose. Mucosal samples were obtained for morphological documentation and immunohistochemical analysis of substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY). Furthermore, the expression of SP and CGRP in the nasal mucosa and trigeminal ganglion of rats after experimental infection with Mycoplasma pulmonis was assessed by immunohistochemistry and Northern blot. In a clinical setting, cytokine patterns and the expression of glucocorticosteroid receptor (GR) mRNA in excised human nasal polyps was estimated by solution hybridization and immunohistochemistry. Tissue from untreated patients was compared to polyps from patients treated with a nasal corticosteroid, budesonide, for two months. Pneumococcal sinusitis was associated with an intense initial inflammatory response while B. fragilis and S. aureus-infections led to a severe, more progressive inflammation with little or no signs of healing during the period studied. Polyps were frequent in experimentally infected mucosa and after treatment with FMLP or agarose. Polyp formation was characterized by initial epithelial damage followed by ingrowth of regenerating, branching epithelial strains and formation of intraepithelial microcavides. Fusion of microcavities lead to separation of the newly-formed polyp from adjacent mucosa Pretreatment with betamethasone caused a delay in polyp formation and a reduced ingrowth of pathogenic bacteria into the sinus. Goblet cells were frequent in infected and capsaicin-treated mucosa and appeared to develop from secretory serous cells via intermediate stages. While topical capsaicin application caused mainly epithelial changes, surgical denervation led to congestion of mucosal glands. Experimental M. pulmonis infection in rats caused increased immunohistochemical expression of SP and CGRP in the mucosa. No difference regarding cytokine immunoreactivity or regulation of GR was seen in polyp tissue obtained from patients given nasal budesonide spray when compared to an untreated group. A reason may be inherent or induced resistance to corticosteroids in the tissue.