Mediators of inflammation in nasal lavage from aspirin intolerant patients after aspirin challenge

Summary 

The pathogenetic mechanisms underlying development of persistent inflammation in aspirin (ASA) intolerance are not fully understood. The aim of this study was to determine levels of MCP-3, RANTES, eotaxin, Il-5 and Il-3 in aspirin intolerant asthmatics (AIA) after nasal lysine–aspirin (Lys–ASA) challenge. Twenty AIA and 10 aspirin tolerant controls (ATC) were challenged with saline or 14.4mg of Lys–ASA. Lys–ASA challenge induced clinical symptoms and influx of eosinophils and basophils only in AIA group. Statistically significant higher levels of MCP-3 and RANTES were found in lavages from AIA as compared with ATC (p<0.05 in all time points). Before challenge the average level of MCP-3 was 86.95pg/ml in AIA and 47.61pg/ml in ATC, RANTES levels were 34.20pg/ml in AIA and 17.21pg/ml in ATC and did not change after the challenge in both group. The mean eotaxin’s level was 11.01pg/ml in AIA and 8.03pg/ml in ATC before and increased to 20.06, 26.22pg/ml (4 and 24h in AIA) as compared to 10.51, 14.76pg/ml (4 and 24h in ATC) after the challenge (p<0.05). Interleukin-3 and Il-5 were not detectable. The highest inhibition of eosinophils’ chemotaxis was induced by anti-eotaxin (47% of inhibition), followed by anti-RANTES (29%), anti-MCP-3 (19%) and anti-Il-5 (9%). In summary, we found that persistent inflammation in AIA patients is characterized by overproduction of MCP-3 and RANTES. Lack of increase in MCP-3 and RANTES levels after Lys–ASA challenge suggest that those mediators are involved in chronic rather than acute phase of ASA induced inflammation.

Keywords: Aspirin (ASA) hypersensitivity, Aspirin challenge, MCP-3, RANTES, Eotaxin

Abbreviations: ASA, aspirin, AIA, aspirin intolerant asthmatics, ATC, aspirin tolerant controls, COX, cyclooxygenase, Cys-LT, cysteinyl leukotriene, Il, interleukin, MCP-3, monocyte chemoattractant protein-3, NSAID, nonsteroidal anti-inflammatory drugs, PG, prostaglandin, 15-HETE, 15-hydroxyeicosatetraenoic acid