Role of Inflammation in Nasal polyposis
Nasal polyp is not simple oedema of the mucous membrane of the lateral nasal wall, instead it is a denovo inflammatory growth of the mucosa of the lateral nasal wall in the area of uncinate process and bulla mucosa.
Characteristic features of nasal polyp include:
1. Basal cell hyperplasia
2. Goblet cell hyperplasia
3. Squamous metaplasia (rare)
Features seen in lamina propria:
4. Degenerated cystic glands filled with mucin
Among the above mentioned factors eosinophils, lymphocytes, and oedema of lamina propria play important roles in the genesis of nasal polyp. Studies have demonstrated that risk of developing nasal polyp may be linked to the small arm of chromosome 6. This area of chromosome 6 contains
1. HLA antigens
3. Heat shock protein
4. Proinflammatory gene – TNF ?
The HLA genes and the proinflammatory genes are transmitted together from parent to offspring.
Role played by Staph aureus exotoxins in the genesis of nasal polyp:
Exotoxins produced by Staph aureus act as super antigens. They stimulate IgE response against them. The presence of Staph aureus exotoxins and IgE response to them are two potent mediators that could trigger the mucosal lining of lateral nasal wall into developing nasal polyp. Studies have also demonstrated that TNF ? levels in patients with nasal polyp was four times more than that present in normal controls. TNF ? is a potent immunomediator and proinflammatory cytokine that has been implicated in a large number of human diseases that include nasal polypi, periodontal diseases, irritable bowel syndrome etc.
Cytokines in nasal polypoid mucosa:
The following cytokines have been demonstrated in large quantities in nasal polyp tissue:
1. TNF ?
3. VCAM – 1
TNF ? and VCAM -1:
TNF ? is produced primarily by macrophages and T cells. It was initially known for its antitumor and cytotoxic activity. Studies have now revealed that they play a vital role in evoking inflammatory process. TNF ? is known to upregulate VCAM – 1 in fibroblasts present in the nasal mucosa. This upregulation takes place via NF-k? pathway in the nasal fibroblast. This upregulation of VCAM -1 in the nasal fibroblasts play a vital role in the pathogenesis of nasal polypi. Hence there is a strong rationale in the use of anti NF-k? drugs in the management of inflammatory nasal polypi. The eosinophils that accumulate in the polypoidal tissue can also synthesize TNF – ? causing the vicious cycle to continue. The presence of TNF-? can increase the secretion of chemokines which attracts eosionphils into the polypoidal tissue.
TNF-? increases the secretion of cotaxin and also expression of RANTES from the fibroblasts present in the nasal polypi.
Role of eosinophil changes in alterations of electrophysiology of nasal mucosa:
The substances produced by eosinophils i.e. Eosinophilic mediator and Major Basic Protein increases the permeability of nasal mucous membrane to water. This is caused due to changes that take place in the sodium gate mechanism present in the mucosal cell wall. This excess permeation of water into the nasal mucosa is the cause for mucosal oedema (the most prominent histopathological findings seen in nasal polypi). Polyp epithelia show increased sodium absorption which in turn is followed by water.