Lipoxin A₄ generation is decreased in aspirin-sensitive patients in lysine-aspirin nasal challenge in vivo model

• Published in: Allergy (Copenhagen) 2009-12, Vol.64 (12), p.1746-1752
• Main Authors: Kupczyk, M, Antczak, A, Kuprys-Lipinska, I, Kuna, P
• Format: Article
• Language: English
• Subjects: Adult; Allergens - administration & dosage; Allergies; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Aspirin - administration & dosage; Aspirin - analogs & derivatives; Aspirin - immunology; aspirin sensitivity; Asthma; Biological and medical sciences; Case-Control Studies; Chronic obstructive pulmonary disease, asthma; Dermatology; Drug Tolerance - immunology; Enzyme-Linked Immunosorbent Assay; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Grasses; Humans; Inflammation - etiology; Leukotriene C4 - analysis; Leukotriene C4 - biosynthesis; lipoxins; Lipoxins - analysis; Lipoxins - biosynthesis; Lys-ASA; Lysine - administration & dosage; Lysine - analogs & derivatives; Medical sciences; Middle Aged; nasal challenge; Nasal Provocation Tests - adverse effects; Nasal Provocation Tests - methods; Nose; Pneumology; Poaceae - immunology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/j.1398-9995.2009.02047.x

Lipoxins represent a group of lipoxygenase derived eicosanoids which, in contrast to leukotrienes, are potent anti-inflammatory mediators. The aim of our study was to determine lipoxin A₄ (LXA₄) and leukotriene C₄ (LTC₄) levels in nasal lavages after intranasal challenge with aspirin in aspirin intolerant (AIA) in comparison to aspirin tolerant (ATA) asthmatics and after allergen challenge in patients suffering from allergic rhinitis. Twelve AIA, 8 ATA and 20 allergic patients were challenged with placebo, 16 mg of lysine-aspirin (Lys-ASA) or allergen (grasses). Nasal lavages were collected and eicosanoids' levels were determined using ELISA. Clinically positive Lys-ASA challenge in AIA resulted in influx of leukocytes (eosinophils and basophils) to nasal secretions and increase of LTC₄ to 106.82 pg/ml (P < 0.05 vs baseline (26.58 pg/ml)) on first hour after the challenge. We did not observe any differences in LTC₄ level before and after ASA challenge in ATA. In AIA group the mean level of LXA₄ was 43 ± 21.5 pg/ml after placebo and decreased in 2 h after Lys-ASA challenge (29 ± 17 pg/ml, P = 0.015). We found an increase in LXA₄ in ATA after ASA provocation as compared to placebo (33 ± 16 pg/ml vs 52 ± 31 pg/ml, P = 0.046). In atopic patients baseline level of LXA₄ was 33.49 ± 16.95 pg/ml with no difference after the clinically positive allergen challenge (36.22 ± 13.26 pg/ml, P = 0.23). Results of our study confirm that AIA have diminished LXs' biosynthesis capacities in vivo after ASA challenge. Taking into consideration anti-inflammatory properties of lipoxins this phenomenon may be partially responsible for the development of chronic inflammation in AIA patients.