Lipoxin A4 generation is decreased in aspirin-sensitive patients in lysine-aspirin nasal challenge in vivo model.
BACKGROUND
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 A(4) (LXA(4)) and leukotriene C(4) (LTC(4)) 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.


METHODS
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.


RESULTS
Clinically positive Lys-ASA challenge in AIA resulted in influx of leukocytes (eosinophils and basophils) to nasal secretions and increase of LTC(4) 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 LTC(4) level before and after ASA challenge in ATA. In AIA group the mean level of LXA(4) 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 LXA(4) 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 LXA(4) 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).


CONCLUSIONS
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.
Kupczyk
M
M
Department of Internal Medicine, Medical University of Lodz, Lodz, Poland.
Antczak
A
A
Kuprys-Lipinska
I
I
Kuna
P
P
D000328:Adult; D000485:Allergens / Q000008:administration & dosage; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology*; D016022:Case-Control Studies; D004361:Drug Tolerance / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007249:Inflammation / Q000209:etiology; D017997:Leukotriene C4 / Q000032:analysis / Q000096:biosynthesis; D044045:Lipoxins / Q000032:analysis / Q000096:biosynthesis*; D008239:Lysine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008875:Middle Aged; D009299:Nasal Provocation Tests / Q000009:adverse effects* / Q000379:methods; D006109:Poaceae / Q000276:immunology
D000485:Allergens; D000894:Anti-Inflammatory Agents, Non-Steroidal; D044045:Lipoxins; C040527:lipoxin A4; D017997:Leukotriene C4; D008239:Lysine; D001241:Aspirin; C010395:acetylsalicylic acid lysinate