Prostaglandin, leukotriene, and lipoxin balance in chronic rhinosinusitis with and without nasal polyposis.
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 C 4 synthase, and 15-lipoxygenase. Enzyme immunoassays were used to measure IL-5, eosinophil cationic protein, and eicosanoid (leukotriene [LT] C 4 , LTD 4 , and LTE 4 ; lipoxin A 4 ; and prostaglandin E 2 [PGE 2 ]) concentrations.


RESULTS
COX-2 mRNA and PGE 2 concentrations were similar in the CRS and NM groups but significantly decreased in nasal polyp tissue, especially in the CRS-ASNP group. LTC 4 synthase, 5-lipoxygenase mRNA, LTC 4 , LTD 4 , and LTE 4 concentrations increased with disease severity among the patient groups. 15-Lipoxygenase and lipoxin A 4 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 LTC 4 , LTD 4 , and LTE 4 concentrations and inversely with PGE 2 concentrations.


CONCLUSIONS
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.
Pérez-Novo
Claudina Angela
CA
Upper Airways Research Laboratory, Department of Otorhinolarynogy, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium. claudina.Pereznovo@UGent.be
Watelet
Jean Baptiste
JB
Claeys
Cindy
C
Van Cauwenberge
Paul
P
Bachert
Claus
C
D000328:Adult; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D002908:Chronic Disease; D051546:Cyclooxygenase 2; D015777:Eicosanoids / Q000378:metabolism; D047150:Eosinophil Cationic Protein / Q000032:analysis; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015848:Interleukin-5 / Q000032:analysis; D015289:Leukotrienes / Q000378:metabolism*; D044045:Lipoxins / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism; D009298:Nasal Polyps / Q000150:complications / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012220:Rhinitis / Q000150:complications / Q000378:metabolism*; D012852:Sinusitis / Q000150:complications / Q000378:metabolism*
D015777:Eicosanoids; D015848:Interleukin-5; D015289:Leukotrienes; D044045:Lipoxins; D008565:Membrane Proteins; D011453:Prostaglandins; D012333:RNA, Messenger; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D005982:Glutathione Transferase; D047150:Eosinophil Cationic Protein; C041116:leukotriene-C4 synthase