Chronic rhinonsinusitis and nasal polyposis: the etiopathogenesis revealed?
Nasal polyps represent a severe eosinophilic inflammation of the upper airways which is characterized by poor impact of therapeutic intervention and frequent recurrences. Based on distinct cytokine, mediator and cell profiles, chronic sinonasal disease in Caucasians can be differentiated into several subgroups such as chronic rhinosinusitis without nasal polyps, chronic rhinosinusitis with nasal polyps, and nasal polyps in cystic fibrosis patients,. In Caucasians, nasal polyps showed a Th2 polarisation with high IL-5 concentrations, while chronic rhinosinusitis without polyps was characterized by a Thl polarisation with high levels of IFN-gamma. In the Caucasian nasal polyps we found that significantly more nasal polyp patients are colonized with S. aureus and that colonization increased in patients with concomitant asthma and aspirin sensitivity. Although there was no major difference in the presence of enterotoxin genes in S. aureus strains derived from nasal polyp or control patients, we found an increased immune response to S. aureus enterotoxins in nasal polyps, which resulted in a more pronounced eosinophilic inflammation and higher total IgE production in those polyps affected. We suggest that S. aureus superantigens amplify the inflammation in about 50% of nasal polyps, resulting in a strong Th2 polarisation, eosinophil activation, and an overproduction of IgG4 and IgE. These findings imply new therapeutic approaches apart from the currently used topical and systemic steroid therapy for nasal polyposis. In three double blind placebo controlled studies it was shown that firstly, oral corticosteroids only led to a short term reduction of polyp size. Secondly that a low dose of doxycycline treatment for 20 days had a sustained clinically relevant effect on polyp size for more than 3 months and thirdly we also showed a significant effect on polyp size by selective antagonizing IL-5 with a monoclonal antibody.
Van Cauwenberge
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Universiteit Gent - Vakgroep neus-, keel-, en oorheelkunde, Upper airways research laboratory, De Pintelaan 185 - B 9000 Gent.
Van Zele
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Bachert
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D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002908:Chronic Disease; D004318:Doxycycline / Q000627:therapeutic use*; D004768:Enterotoxins / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000276:immunology; D015848:Interleukin-5 / Q000037:antagonists & inhibitors; D009298:Nasal Polyps / Q000209:etiology* / Q000382:microbiology / Q000517:prevention & control; D012852:Sinusitis / Q000209:etiology* / Q000382:microbiology / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology*
D000911:Antibodies, Monoclonal; D004768:Enterotoxins; D007074:Immunoglobulin G; D015848:Interleukin-5; D018089:Superantigens; D007073:Immunoglobulin E; D004318:Doxycycline