Prostaglandin, leukotriene, and lipoxin balance in chronic rhinosinusitis with and without nasal polyposis

doi:10.1016/j.jaci.2005.02.029

Journal of Allergy and Clinical Immunology

Volume 115, Issue 6, June 2005, Pages 1189-1196

https://doi.org/10.1016/j.jaci.2005.02.029 Get rights and content

Background

Upper airway diseases and especially the aspirin hypersensitivity syndrome have been linked to changes in the arachidonic acid cascade; however, the specificity of these changes and their relation to inflammatory reactions in these diseases still remain controversial.

Objective

We aimed to study the tissue eicosanoid production in 3 subgroups of patients with chronic rhinosinusitis (CRS) and control subjects and to correlate it with the severity of inflammation and clinical manifestation of aspirin sensitivity.

Methods

Samples were prepared from sinonasal tissue of patients with CRS with (CRS-NP group, n = 13) and without nasal polyposis (CRS group, n = 11), sinonasal tissue of patients with nasal polyposis and aspirin sensitivity (CRS-ASNP group, n = 13), and normal nasal mucosa from healthy subjects (NM group, n = 8). Real-time PCR was applied for mRNA quantification of COX-2, 5-lipoxygenase, leukotriene C₄ synthase, and 15-lipoxygenase. Enzyme immunoassays were used to measure IL-5, eosinophil cationic protein, and eicosanoid (leukotriene [LT] C₄, LTD₄, and LTE₄; lipoxin A₄; and prostaglandin E₂ [PGE₂]) concentrations.

Results

COX-2 mRNA and PGE₂ concentrations were similar in the CRS and NM groups but significantly decreased in nasal polyp tissue, especially in the CRS-ASNP group. LTC₄ synthase, 5-lipoxygenase mRNA, LTC₄, LTD₄, and LTE₄ concentrations increased with disease severity among the patient groups. 15-Lipoxygenase and lipoxin A₄ concentrations were increased in all CRS groups compared with in the NM group but were significantly downregulated in the CRS-ASNP group when compared with the CRS-NP group. IL-5 and eosinophil cationic protein were increased in both groups of nasal polyp tissue compared with in the NM and CRS groups and correlated directly with LTC₄, LTD₄, and LTE₄ concentrations and inversely with PGE₂ concentrations.

Conclusion

Changes of tissue eicosanoid metabolism do occur in CRS, even in the absence of clinical aspirin sensitivity, and these changes appear to be related to the severity of eosinophilic inflammation.

Section snippets

Patients

Study subjects were selected on the basis of a documented medical history for CRS; a pathologic endoscopy, computed tomographic (CT) scan, or both; and the failure of 3 weeks of drug therapy (combined administration of antibiotics and oral glucocorticoids, 32-mg down to 8-mg daily dosage) to persistently relieve symptoms of this condition. Samples from ethmoidal and maxillary sinuses were collected from patients during functional endoscopic sinus surgery procedures in the Department of

mRNA expression by means of quantitative real-time PCR

Results of the quantitative real-time PCR are summarized in Fig 1. COX-2 expression was similar between the CRS and NM groups but was significantly downregulated in both nasal polyp groups (P = .0002), with a further decrease in the CRS-ASNP group compared with that seen in the CRS-NP group (P < .05). 15-LO mRNA expression was significantly increased in all patients with CRS compared with in healthy subjects (P = .0018). Interestingly, the CRS-ASNP group showed a downregulation of this enzyme

Discussion

The development of aspirin sensitivity remains unclear and has been related to several processes, including changes in AA metabolism, allergy, viral infection, and severity of inflammation.32, 33 We here show that COX-2 mRNA and PGE₂ concentrations were significantly decreased in nasal polyp tissue, especially in patients with aspirin sensitivity (CRS-ASNP group). In contrast, the lowest levels of LTC₄S, 5-LO mRNA, LTC₄, LTD₄, and LTE₄ were observed in control subjects, and the highest levels

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Supported in part by grant BOF: 011D02903 given to Claudina A. Pérez-Novo by the University of Ghent.

Disclosure of potential conflict of interest: C. A. Pérez-Novo received a grant (BOF: 011D02903 [2003-2005]) from the University of Ghent, Belgium, which partially supported this work. P. Van Cauwenberge—none disclosed other than the grant received by C. A. Pérez-Novo.

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Rhinitis, sinusitis, and ocular diseasesProstaglandin, leukotriene, and lipoxin balance in chronic rhinosinusitis with and without nasal polyposis

Background

Objective

Methods

Results

Conclusion

Section snippets

Patients

mRNA expression by means of quantitative real-time PCR

Discussion

Trends Pharmacol Sci

Ann Allergy Asthma Immunol

J Allergy Clin Immunol

Otolaryngol Head Neck Surg

J Allergy Clin Immunology

J Allergy Clin Immunol

FEBS Lett

J Allergy Clin Immunol

Prostaglandins Leukot Essent Fatty Acids

Otolaryngol Head Neck Surg

Methods

J Allergy Clin Immunol

Prostaglandins

J Biol Chem

Current estimates from the National Health Interview Survey. United States, 1985

Vital Health Stat

Nasal polyposis and sinusitis

Epidemiology of nasal polyps

Allergy Asthma Proc

Intolerance to aspirin

Ann Intern Med

Natural history of aspirin-induced asthma. AIANE Investigators. European Network on Aspirin-Induced Asthma

Eur Respir J

Rhinitis, sinusitis, and ocular diseases
Prostaglandin, leukotriene, and lipoxin balance in chronic rhinosinusitis with and without nasal polyposis